workshop on metabolomics in the context of ...ferredoxin p700+ 4fe-4s p700 on excitation p700...

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WORKSHOP ON METABOLOMICS IN THE CONTEXT OF SYSTEMS BIOLOGY: A RATIONAL APPROACH TO SEARCH FOR LEAD MOLECULES 25-26/02/10 Maria Fátima das Graças Fernandes da Silva Federal University of São Carlos, SP, Brazil [email protected]

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Page 1: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

WORKSHOP ON

METABOLOMICS IN THE CONTEXT OF

SYSTEMS BIOLOGY: A RATIONAL APPROACH

TO SEARCH FOR LEAD MOLECULES

25-26/02/10

Maria Fátima das Graças Fernandes da Silva

Federal University of São Carlos, SP, Brazil

[email protected]

Page 2: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

NATURAL PRODUCTS

AND PHOTOSYNTHESIS

INTERACTION

N

O

OH

OH

OMe

O

OH

Me

N

O

OH

OOH

OH

OMeMe

AcO

O

H

OH

Page 3: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Photosynthesis is the primary

metabolic process disrupted by a

diverse range of herbicides.

However, other targets for herbicide action are

cell division, cell elongation, plant growth regulation

metabolism and biosynthesis of lipids, amino acids

and pigments.

Page 4: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

As part of our efforts to find

potential lead compounds as herbicides,

we have been assayed natural products

as inhibitors of photosynthesis.

N

O

OH

OH

OMe

O

OH

Me

N

O

OH

OOH

OH

OMeMe

AcO

O

H

OH

Page 5: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Photosynthesis in green plants is mediated by two

linked photosystems: Photosystem II and I

Photosystem II, begins

with excitation of a special

pair of chlorophyll

molecules that are bound

by D1 and D2 subunits of

proteins system.

D1 D2

Thylakoid

membrane

Page 6: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

The special pair of

chlorophyll a molecules absorb

light at 680 nm, thus it is

often called P680.

On excitation P680 rapidly

transfers an electron to a

pheophytin, which transfers it

to a bound plastoquinone at

site QA and then to a mobile

plastoquinone at site QB.

N

H

N

H

OMe

OO

N

N

H

H

O

H

O O

R

O

On

(n = 6 to 10)

O

On

(n = 6 to 10)

Light

QA

QB

MnO4

H2O O2

e-

P680* P680+

Page 7: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

With the arrival of a

second electron and the

uptake of two protons, the

mobile plastoquinone is

reduced to QH2

O-

O.n

(n = 6 to 10)

e-

O-

O- n

(n = 6 to 10)

H+2OH

OH n

(n = 6 to 10)

N

H

N

H

OMe

OO

N

N

H

H

O

H

O O

R

O

On

(n = 6 to 10)

Light

QA

QB

MnO4

H2O O2

O-

O- n

(n = 6 to 10)

e-

P680*P680+

Page 8: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

O

NH

NH-O

O

NH

NH.O

e-_

N

H

N

H

OMe

OO

N

N

H

H

O

H

O O

R

O

On

(n = 6 to 10)

O

On

(n = 6 to 10)

Light

QA

QB

e-

P680*

2 H2O + (Mn2+, Mn3+, Mn4+, Mn5+) O2 + 4 e- + 4 H+

O

NH

NH-O

O

NH

NH.O

e-_ P680+

The pair P680+

extracts electrons

from tyrosine

residue of subunit

D1 of PSII.

Oxidized tyrosin

removes electrons

from water

molecules bound to

the manganese

center.

Page 9: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Photosystem II

occurs in the thylakoid

membrane.

The manganese

center, or the water

oxidation occurs in the

thylacoide lumen

Stroma

Lumen

4H+

4H+

+ 4e-

Page 10: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

In short

Electrons flow from H2O to QB (QH2)

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tia

l (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QB

Photosystem II

O2

Page 11: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Cytochrome bf links Photosystem

II to Photosystem I

This complex catalyzes the

transfer of electrons from

plastoquinol (QH2) to plastocianin

(Pc), a small, soluble copper protein

in the thylakoid.1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QB

Photosystem II

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QB

Photosystem II

O2

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QB

Photosystem II

O2

PQ

Page 12: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Plastoquinol is oxidized to plastoquinone

(n = 6 to 10)

n

OH

OH

- H+

O-

OH n

(n = 6 to 10)

O.

OH

Cytochrome bf (Fe-S protein) PCox PCred

O.

O

- H+(n = 6 to 10)

n

O

O

_ e-

_ e-

(n = 6 to 10)

n

n

(n = 6 to 10)

The electrons flow through the iron-sulfur protein

of Cytochrome bf complex to convert oxidized

plastocyanin into its reduced form.

Page 13: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

(n = 6 to 10)

n

OH

OH

- H+

O-

OH n

(n = 6 to 10)

O.

OH

Cytochrome bf (Fe-S protein) PCox PCred

O.

O

- H+(n = 6 to 10)

n

O

O

_ e-

_ e-

(n = 6 to 10)

n

n

(n = 6 to 10)

Stroma

Lumen

4H+

4H+

+ 4e-

These

protons are

released in the

thylakoide

lumen

Thylakoide lumen low pH

Page 14: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

In short

Electrons flow from H2O to Plastocyanin, then to PSI

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tia

l (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

Pc

Photosystem II

O2

PQ

Photosystem I

Page 15: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Photosystem I, begins with excitation of a special

pair of chlorophyll a molecules that are bound by

psaA and psaB subunits of proteins system.

The special pair of chlorophyll a molecules absorb light

at 700 nm, thus it is often called P700.

PsaAPsaB

Page 16: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Light

e-

P700*

Chlorophyll

(A0)

Quinone

(A1)

Ferredoxin

P700+

4Fe-4S

P700

On excitation P700

rapidly transfers an

electron to chlorophyll at

site A0, which transfers it

to quinone at site A1 and

then to a set of iron (Fe)-

Sulfur clusters, and

finally to ferredoxin (Fd) .

Photosystem I

Page 17: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Light

e-

P700*

Chlorophyll

(A0)

Quinone

(A1)

Ferredoxin

P700+

Plastocyanin (Cu+)

Plastocyanin (Cu2+)

e-

4Fe-4S

P700

P700+ captures

an electron from

reduced

plastocyanin to

return to P700.

PSII

Page 18: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Ferredoxin transfers electrons to NADP+ and

the reaction is catalyzed by ferredoxin-NADP+

reductase to form NADPH

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tia

l (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

*

Page 19: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

The excess of protons flow out of

lumen through ATP synthase to

generate ATP from ADP and Pi in the

stroma.

ATP synthase is called

CF1-CF0 complex

Photosynthesis

*

Page 20: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

A number of compounds isolated in our own

investigations of plants from Sapindales (Rutales)

were assayed.

Inhibition of photophosphorylation and

electron transport chain in thylakoids by

Natural Products

Page 21: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

We use artificial electron donors and

acceptors, which bind in specific site of PSII or

PSI

e-

.

N

N

N

N

Paraquat

Methylviologen (MV)

MV

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 22: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Measurement of ATP Synthesis

We use

methylviologen

(MV) as electron

acceptor, and

chlorophyll from

the intact

chloroplasts

freshly lysed.

Stock solution of NP is prepared using DMSO.

MV

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 23: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

We analyzed the effect of N P on electron

transport from H2O to MV.

First of all, we measure the proton concentration,

or ATP synthesis

ATP

MV

Page 24: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Photosynthetic phosphorylation from water to MV

as electron acceptor was inhibited by siderin in a

concentration-dependent manner.

Effect of compounds 1 (), 2 (), 3 (), and 4 () on ATP synthesis.

O OMeO

OMe

1

Veiga, da Silva et al, Arch. Biochem. Biophys. 465, 38-43, 2007

Page 25: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

The I50 value for siderin (1) was 27.0 M.

The other coumarins were almost inactive as

inhibitor to ATP synthesis.

Effect of compounds 1 (), 2 (), 3 (), and 4 () on ATP synthesis.

O OMeO

OMe

1

O OMeO

MeO

O OO

OMe

O O

OMe

O

2

3

4

Page 26: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

We measure the oxygen concentration with an

oxygen electrode (Clark-type electrode)

Measurement of non-cyclic electron transport

MV

Page 27: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Siderin inhibited the phosphorylating electron

transport rate 100% at 400 M.

Effect of siderin on electron flow [basal (), phosphorylating (),

and uncoupled ()] from water to MV in spinach chloroplasts

O OMeO

OMe

1

Page 28: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

We use artificial electron donors and acceptors,

which bind in specific site of PSII or PSI

LOCALIZATION OF SIDERIN SITES OF

INTERACTION ON PSII OR PSI

ELUCIDATION OF THE MECHANISM OF ACTION

MV

Page 29: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Dichlorophenol-

indophenol

DCPIPox DCPIPred

H2O

We analyzed the effect

of siderin on electron

transport from H2O to

DCPIPox; then to QB.

We measure the oxygen

concentration with an

oxygen electrode (Clark-

type electrode)

2 H+

e-

OH

ClCl

OH

N H

O

N

ClCl

OH

DCPIPox

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 30: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

We also add

DBMIB, which

binding in

Cytochrome bf

complex,

inhibiting the

electron

transport from

H2O to Quinone

pool (Qp).

O

O

Br

Br2,5-dibromo-3-methyl-

6-isopropyl-p-benzoquinone

Then, electrons flow to DCPIPox.

DCPIPox

Page 31: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1 Conc. M

0

100

200

300

400

PSII

H2O to DCPIPox (%)

100

78

70

52

0

Siderin inhibits electron transport

from H2O to DCPIPox, then to QB, by

100% at 400 M

Veiga, da Silva et al, Arch. Biochem. Biophys. 465, 38-43, 2007

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

DCPIPox

Page 32: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

MnO4

H2O O2

MnO4

H2O O2

P680+

P680Donor site

Acceptorsite

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

DCPIPox

Page 33: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

MnO4

H2O O2

MnO4

H2O O2

P680+

Donor site

SiMo

To localize the

siderin site of

interaction on

PSII between H2O

to QB, we use

electron acceptor

which binds in the

donor site of

PSII, as

silicomolybdate.

SiMo12O-4

40 + 2e- + 2 H+ H2SiMo12O-4

40

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial

(V)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 34: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

MnO4

H2O O2

MnO4

H2O O2

P680+

Donor site

SiMo

SiMo12O-4

40 + 2e- + 2 H+ H2SiMo12O-4

40

DCMU

N

Cl

Cl

N

O

H

We also add

DCMU, which binding

in plastoquinone site,

inhibiting the

electron transport

from H2O to QB.

Then, electrons flow to SiMo.

Dichlorophenyldimethylurea

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 35: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

MnO4

H2O O2

MnO4

H2O O2

P680+

Donor site

SiMo

1 Conc. M

0

100

200

300

400

PSII

H2O to SiMo (%)

100

75

50

12

0

Siderin inhibits electron transport from

H2O to SiMo by 100% at 400 M

DCMU

Veiga, da Silva et al, Arch. Biochem. Biophys. 465, 38-43, 2007

1.0

0.0

- 1.0R

ed

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0R

ed

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0R

ed

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 36: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

MnO4

H2O O2

MnO4

H2O O2

P680+

Donor site

DPC To confirm the siderin site

of interaction on PSII between

H2O to P680+, we use electron

donor which bind in the donor

site of PSII, as DPC,

diphenylcarbazide.

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 37: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

MnO4

H2O O2

MnO4

H2O O2

P680+

Donor site

DPC

With DPC, we use Tris-

treated chloroplasts that inhibit

the water-oxidation enzyme

activity, thus we do not have

the electron flow from water,

but from DPC.

X

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 38: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

2 H+

e-

OH

ClCl

OH

N H

O

N

ClCl

OH

MnO4

H2O O2

MnO4

H2O O2

P680+

Donor site

DPCX

DCPIPox

We analyzed the effect of siderin

on electron transport from DPC to

DCPIPox; then to QB.

O

O

Br

Br

DBMIB

Dichlorophenol -

indophenol

DCPIPox DCPIPred

DPC

Page 39: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Reaction of electron transport from DPC

(diphenylcarbazide) to DCPIPox:

O

N

ClCl

OH OH

ClCl

OH

N H

e-

2 H+

2

- 2 H+

e-

e-

NN N

N

OH

H H

H

NN N

N

O

H

H

NN N

N

O

H

H

2e-

Reduction of DCPIPox

is quantified

spectrophotometrically

at 600 nm.

MnO4

H2O O2

MnO4

H2O O2

P680+

DPCX

Page 40: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

MnO4

H2O O2

MnO4

H2O O2

P680+

Donor site

DPCX

1 Conc. M

0

50

100

200

PSII

DPC to DCPIP (%)

100

83

58

57

Electron transport from DPC to

DCPIPox was partially inhibited at

all concentrations tested.

DCPIPox

Veiga, da Silva et al, Arch. Biochem. Biophys. 465, 38-43, 2007

1.0

0.0

- 1.0R

ed

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0R

ed

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0R

ed

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 41: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1 Conc. M

0

50

100

200

PSII

DPC to DCPIP (%)

100

83

58

57

1 Conc. M

0

100

200

300

400

PSII

H2O to SiMo (%)

100

75

50

12

0

The two results indicated that the target of

siderin is located at the donor and acceptor

sides of PSII, between P680 to QA.

Page 42: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

However, siderin did not affect PSI

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tia

l (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Veiga, da Silva et al, Arch. Biochem. Biophys. 465, 38-43, 2007

Page 43: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

N

O

O

Me

N-methylflindersine does not inhibit electron

transport from H2O to SiMo, but inhibited electron

transport from DCP to DCPIP.

N-Me-Flindersine

Veiga, da Silva et al, Allelopathy J. 21, 133-144, 2008

Page 44: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Thus, the results

indicated that the target

of N-methylflindersine is

located at the acceptor

side of PSII, between QA

and QB.

Cytochrome

bf complex

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QB

Photosystem II

O2

PQ

Veiga, da Silva et al, Allelopathy J. 21, 133-144, 2008

Page 45: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

We analyzed the effect of N-methylflindersine on

electron transport from PSII using TMQH2 to MV.

Localization of N-methylflindersine sites of

interaction on PSI

TMQH2MV

Page 46: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

We also add DCMU, which binding in

plastoquinone site, inhibiting the electron transport

from H2O to QB, or PSI.

Then, electrons flow from TMQH2 to MV.

DCMU

N

Cl

Cl

N

O

HTMQH2

MV

Page 47: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

OHOH

OH

HO OH

O OHOH

OH

-O O

-

O

- 2 H+

OHOH

OH

.O O

.

O

- 2 e-

OHOH

OH

O O

O

+ 2H+

+ 2e-

O

O

OH

OH

- 2e-

O

O

- 2H+

2+ 2e

-

.

N

N+

+N

N

2

+

Ascorbic acid

TMQ TMQH2

Methylviologen (MV)

Tetramethylhydroquinone

(TMQH2) is oxidized to

tetramethylquinone and

transfer electrons to MV.

Page 48: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

2MV.+ 2O2 2MV2+ + 2O2.-

2MV.+

.

N

N+

2

O2

O2.-

O2.-

OHOH

OH

HO OH

O OHOH

OH

-O O

-

O

- 2 H+

OHOH

OH

-O O

.

O

- e-

2H+

H2O2

Hydrogen peroxide

The oxygen

concentration

decrease.

Page 49: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

We measure the oxygen

concentration with an oxygen

electrode (Clark-type electrode)

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

DCMU

N

Cl

Cl

N

O

HTMQH2

MV

O2

O2.-

O2.-

OHOH

OH

HO OH

O OHOH

OH

-O O

-

O

- 2 H+

OHOH

OH

-O O

.

O

- e-

2H+

H2O2

The oxygen concentration

decrease.

Page 50: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

2 Conc. M

0

100

200

300

400

500

PSI

TMQH2 to MV (%)

100

82

73

45

36

0

At 500 M N-methylflindersine

completely inhibited electron

transport from TMQH2 to MV.

Localization of N-methylflindersin sites of

interaction on PSI

Veiga, da Silva et al, Allelopathy J. 21, 133-144, 2008

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

DCMU

N

Cl

Cl

N

O

HTMQH2

MV

Page 51: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Localization of N-methylflindersin sites of

interaction on PSI

We analyzed the effect of N-methylflindersine

on electron transport from Cy bf complex using

DCPIPred to MV; then to 4Fe-4S.

2 H+

OH

ClCl

OH

N H

O

N

ClCl

OH

- e-

Dichlorophenol-

indophenol

DCPIPred

DCPIPredMV

DCMU

N

Cl

Cl

N

O

H

Page 52: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Localization of N-methylflindersin sites of

interaction on PSI

2 Conc. M

0

100

200

300

400

500

PSII

DCPIPred to MV (%)

100

-

100

100

-

-

N-methylflindersine did

not inhibit electron transport

from DCPIPred to MV.

Veiga, da Silva et al, Allelopathy J. 21, 133-144, 2008

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

DCPIPredMV

DCMU

N

Cl

Cl

N

O

H

Page 53: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

*

*

Thus N-methylflindersine has two sites of

interaction and inhibition, one where QB interacts

and the second one is at PQH2 oxidation site.

Localization of N-methylflindersin sites of

interaction on PSI

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Re

du

cti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 54: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

Several natural products isolated for our group have

been evaluated as inhibitor of photophosphorylation

and electron transport chain in thylakoids.

Among the 200 compounds evaluated, only 16 were the

most active:

Veiga, PhD Thesis, UFSCar, Brazil, 2008

Page 55: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

ATP synthesis inhibition by:

I50 26.0 M

N

O

O

H

I50 48.0 M I50 46.0 M

I50 61.5 M

I50 82.0 M

N O

OMe

MeO

OMe

N O

OMe

MeO

MeO

N O

OMe

MeO

N O

OMe

OMe

MeO

Page 56: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

ATP synthesis inhibition by:

N

O

OH

OH

OMe

O

OH

Me N

O

OH

OOH

OH

OMeMe

N

O

OH

OH

OH

Me

N

O

OH

OH

OH

OMeMe

N

O

OH

OH

OH

Me

I50 3.3 M I50 6.5 M

I50 33.0 M

I50 24.0 MI50 43.4 M

Page 57: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

ATP synthesis inhibition by:

AcO

O

H

OH O

H

OH

O

O

O

OH

H

HO

H

OH

O

O

HO

OH

I50 6.8 M I50 16.7 M

I50 13.1 MI50 22.7 M

Veiga, PhD Thesis, UFSCar, Brazil, 2008

Page 58: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

N

O

OH

OH

OH

Me

N

O

OH

OH

OH

OMeMe

Localization of compounds sites of interaction on PSII

I50 33.0 MI50 24.0 M

The results indicated that the targets of

these compounds are located at the donor and

acceptor sides of PSII, between P680 to QA.

O

H

OH

O

I50 16.7 MO

O

HO

OH

I50 22.7 M

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 59: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

The results

indicated that the

actions of these

compounds are

located at the

acceptor side of

PSII, between QA

and QB.

Localization of

compounds sites of

interaction on PSII

I50 26.0 M

N

O

O

HI50 48.0 M

I50 46.0 M

N O

OMe

MeO

OMe

N O

OMe

OMe

MeO

I50 61.5 M

N O

OMe

MeO

MeO

I50 82.0 M

N O

OMe

MeO

Page 60: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

In contrast, dihydropyranoacridones and

dihydrofuroacridones have the site of

interaction and inhibition at Cy bf complex.

Localization of

compounds sites of

interaction on PSI

N

O

OH

OH

OMe

O

OH

MeN

O

OH

OOH

OH

OMeMeI50 3.3 M

I50 6.5 MVeiga, PhD Thesis, UFSCar, Brazil, 2008

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

ucti

on

po

ten

tial (V

)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Lumen4 H+

Page 61: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

DCMU

N

Cl

Cl

N

O

H

Many commercial

herbicides kill weeds by

interfering with the

action of PSII or PSI.

PSII inhibitors include

urea derivatives, such as

diuron (DCMU), one of

the most sold herbicides.

The mechanism of action

of these compounds were

similar to DCMU.

O OMeO

OMe

N

O

OH

OH

OH

Me

N

O

OH

OH

OH

OMeMe

I50 27.0 MI50 33.0 MI50 24.0 M

O

H

OH

O O

O

HO

OH

I50 22.7 MI50 16.7 M

1.0

0.0

- 1.0

Red

uctio

n po

tent

ial (

V)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Thylakoid lumen

4 H+

1.0

0.0

- 1.0

Red

uctio

n po

tent

ial (

V)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

uctio

n po

tent

ial (

V)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Thylakoid lumen

4 H+

Concluding Remarks

Page 62: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

DCMU

N

Cl

Cl

N

O

H

O OMeO

OMe

N

O

OH

OH

OH

Me

N

O

OH

OH

OH

OMeMe

I50 27.0 MI50 33.0 MI50 24.0 M

O

H

OH

O O

O

HO

OH

I50 22.7 MI50 16.7 M

1.0

0.0

- 1.0

Red

uctio

n po

tent

ial (

V)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Thylakoid lumen

4 H+

1.0

0.0

- 1.0

Red

uctio

n po

tent

ial (

V)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

1.0

0.0

- 1.0

Red

uctio

n po

tent

ial (

V)

Mn

center

H2O

P680

Photon 1

P680*

Ph

QA

QBCytochrome

bf complexP700

P700*

Pc

Photon 2

A0

A1

4Fe-4S

Fd-NADP+

reductase

NADPH

Photosystem II

Photosystem I

O2

PQ

Thylakoid lumen

4 H+

Concluding Remarks

If its assumed that it

is possible to modify the

chemical structure of

compounds to improve

activity, our results are

so good.

Experiments in vivo are

in progress.

Page 63: WORKSHOP ON METABOLOMICS IN THE CONTEXT OF ...Ferredoxin P700+ 4Fe-4S P700 On excitation P700 rapidly transfers an electron to chlorophyll at site A 0, which transfers it to quinone

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