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Introductor BioloLecture 2

School of Biological Sciences

anyang ec no og ca n vers y

ugus

1

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The Origin of Life

Earliest evidence of life: ~3.5 billion years ago

Fossils embedded in rock dated to the time

Found in Australia and Africa.

Age of Earth (and the Solar. .

Age of the Universe (big bang)

11.5 20 billion ears a o.

Within the first 1 billion years,

microorganisms came about.

emar a e s nce mos o e me

the Solar System was too violent for

any sufficiently stable condition for

Gamow

(1904-1968)Sir Fred Hoyle

-

e o evo ve. ny ng a ma e a

start could easily be destroyed.

-

2

,

leading to formation of a moon or two.

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Our Universe ~ 1050 tonnes of matter

(1 tonne = 1000 kg).

Big Bang: too hot for atoms.

Only elementary particles including protons, neutrons, electrons.

Uniformity implies order; in the cosmic scale of things, there

.

Collapse of hydrogen by gravity leads to the formation of stars,

w ere grav a ona energy orces e a oms o pac so g

that other elements, by nuclear reactions, began to form (in the

stars): first helium, later heavier elements. Release of energy,, .

Fate of primary stars (population II) vary - mostly dependent on

3

s ze, u ma e y eav ng e n e r s w eav er e emen s.

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ur un: secon or r genera on s ars popu a on , us ourplanet has the heavier elements (including carbon) necessary for

the kind of life we are.

98% of the matter collapsed into a single mass, which is the Sun

(1.39 x 106 km in diameter, 1.99 x 1030 kg). Other found ways to.

Closer to the Sun favours heat resistant silicates, farther out allows

g er mo ecu es o con ense, nc u ng wa er.

Violent nature of the early solar system resulted in the ejection and

cap ure o n erp ane ary ma er a , e or g n o ear s roc y crus an

water are likely to be of planetary and cometary origin.

as s gn can mpac o a me eor e ~ mya, ex nc on o

dinosaurs. Worldwide deposition of a layer of the rare layer of

iridium. Giant crater (Chicxulub) under Mexico 180 km across,

4

.

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The Chicxulub Crater in Mexica

The impact asteroid: at least 10 km in diameter

Size of the Chicxulub Crater: 180 km in diameter

y :

Most powerful man-made explosive device: 50 megatons

Consequences:

Mega Tsunamis

EarthquakesVolcanic Eruptions

Dusts cover ~10 years

5

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Venus Earth Mars

r x m

Diameter (km) 12 756

24

12 104

24

6 794

23 .. .

Atmosphere 90 1 0.01

omponen o m 2(mostly)

2

N2 (2.7%)2

O2 (21%)

Surface 71 water H SO Ice/CO ca s

Surface temp Ave ~ 15C Ave ~ 55C>450C

6Deimos

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The Origin of Life and the Primordial Soup

You expressed quite correctly my views where you said

that I had intentionally left the question of the Origin of

present state of our knowledge. Charles Darwin

Ultra vires : beyond the power

some warm little pond, with all sorts of ammonia and

phosphoric salts, light, heat, electricity, etc, DarwinDarwin

(1809-1882)

chemical complexification.

A.I. Oparin and J.B.S. Haldane

(1920s), the little pond was taken

to the Earths entire oceans as thesetting, which reached the

consistency of hot dilute soup

later stuck as described as the

7

primordial soup.

Aleksandr Oparin(1894-1980)

John Haldane(1892-1964)

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The Miller-Urey Experiment (1953, University of Chicago)

Harold Urey Stanley Miller (1893-1981)

Nobel Prize 1934

(1930-2007)

8

Deuterium

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9

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The Miller-Ure ex eriment: results

10

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Problems of the Miller-Urey experiment:

oug o e car on n me ane was conver e o more

complex compounds, the experiment was performed in an

enclosure.

The ingredients in the primordial soup would be too dilute to

encourage reaction (assembly).

The mixture of nitrogen, ammonia, carbon dioxide, carbonmonoxide, methane and hydrogen probably did not represent the

composition of early earth. Geologists now believe that

ammonia, methane, and hydrogen probably did not present in

abundance. Current estimate, the early atmosphere was mostly

carbon dioxide and nitrogen.

Life in the primordial soup was difficult to survive as Earth was

constantly under bombardment until about 200 million years ago.

11

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Chelyabinsk Oblast: 15 February 2013

Size: estimate to be ~18 m, 9,000 tonnesBroke apart ~25 m above ground

~1,500 injuries

Meteor NOT detected

Chebarkul

Lake

2012 DA14: 20 x 40 m (asteroid)

Closest to Earth on 15 Feb 2013, 34,000 km from Centre of

12

, ,

High Earth Orbits of artificial satellites above 35,000 km.

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Barringer Crater: 1.2 km across

100 m deep, 30 000 years old

Extinction of dinosaurs

65 million years ago

Oldest fossil

Multicellular

Or anismsImpactor: 500 km in diameter

Crater: 1500 km across and 50 km deep

Oceans boiled dry: all lives obliterated

End of serious bombardment at

less than 10 million years intervals:yr o mo en roc rop e ra n

2000 yr of normal rain.200 million years ago.

Next 2 slides

13

600 million years

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Catastrophes Affecting Evolution

14

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Catastrophe and Extinction

15

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Black smokers: hydrothermal

vents that can reach

temperature of 350C.Hydrogen sulphide and other

minerals spew out of the cracks

in the Earths crust, able to

catalyze the conversion of

nitrogen to ammonia and morecomplex molecules.

In line with the characterization

o ex remop es a e o

survive and reproduce at

temperatures of over 100C

Deep sea vents in rock strata

could also offer protection

Earliest microbes likely to

.

16

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A prebiotic simulation of a black smoker with pieces of minimal rich lava

with seawater. When superheated, minerals from lava with carbon

dioxide move to a second chamber where the chemicals react to form

17

simple organic molecules.

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Even if we assume that organic molecules can be generated, how they

.

Life is not free reactions of molecules. Certain set of molecules

have to be packaged into a unit that can reproduce.

As far as we know, the package is inside a membranous structure.

However, once it started, the rest should be quite easy.

A protocell-like vesicle that self-

assembles from sim le or anic

molecules in a similar way doesntneed proteins to transport molecules

across its membranes.

Dreamer DW. (2008) How leaky were pr imit ive

, - .

Mansy SS et al (2008) Template-directed

synthesis of a genetic polymer in a model

18

protocell. Nature 454, 122-125

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Geological Timescale (in MYA) and the Evolution of Life on Earth

4600 MYA Formation of Earth (and our Solar System)

3500 MYA Oldest fossils of rokar otes

2200 MYA Cyanobacteria

2000 MYA Oxygen in atmosphere oss s o eu aryo es

850 MYA Multicellular organisms

600 MYA Animal and land lants

490 MYA Cambrian explosion440 MYA Vascular plants

ony s , e rapo s, nsec s

200 MYA Dinosaurs

140 MYA Flowering plants, birds, marsupial mammals

20 MYA First primates

65 MYA Extinction of dinosaurs

19MYA = mill ions of years ago

.

0.25 MYA Homo sapiens

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Whatever the origin is, we can be certain that all living

organisms today has the same origin.

Basic building raw materials proteins, nucleic acids,y , .

We can cross-feed each other.

Same genetic code and material.

With this argument, did life start only once? Not necessarily,

since the other forms simply went extinct and cannot be

detected now.

20

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Earliest Classification System

Plants Animals

Microorganisms

Current Classification System

Bacteria Archaea Eukarya

Protista Fungi Plantae Animalia

21

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Fig. 1.7

22

Anything else

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Further properties of water how would other molecules behave in water?

How to define a concentration?

Carbon: 6 protons and 6 neutrons: atomic weight = 12

Backtrack to counting: The concept of one mole

Avogadro's number: 6.0221415 x 1023

1 mole = the number of atoms in 12 gm of carbon

1 mole (of anything) = 6.0221415 x 1023 (of anything)

It makes the most sense for defining the Avogadros number as the number of

atoms in 1 gm of hydrogen. However, the weights of a proton and a neutron

are not the same, and the electron also affects the weight. At one point,carbon, as shown, were picked as the standard, but it appears NOT to be the

most current definition. Whereas we may leave the details to those who work

in area requiring such precision, we can use the approximation of the atomic

=

23

.

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Water: H O Molecular Weight of water

cc = cubic centimetremeasurement of size

= 2 x (H) + 1 x (O)

= 2 x 1 + 16

= 18

1 litre of liquid = 1000 cc

1 milli-molar = 1 mM = 10-3 M

1 mole of water = 18 gm

6 x 1023 molecules of water = 18 gm

1 micro-molar = 1

M = 10-6 M

1 nano-molar = 1 nM = 10-9 M

Density of water = 1 gm/cc = 1 kg/litre

1 kg of water = = 55.5 mole1000 gm

18 gm/mole

Thus 55.5 mole of water in 1 litre = 55.5 molar

24

The molarity of water = 55.5 mole/litre = 55.5 M

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Water: 1 kg/litre (1 gm/ml)How to make a glucose solution of 5% w/v?

= w v

50 gm glucose + 1 litre of water

OR

gm g ucose n wa er o a na vo ume o re

For dilute solutions: both are the same thing

What is the concentration of glucose at 5% w/v?

Formula of glucose = C6H12O6

Molecular weight of glucose

= (6 x 12) + (12 x 1) + (6 x 16)

1 mole = 180 gm1 gm = 1/180 mole

= 180

5% w/v = 50 gm/litre

== 0.278 mole/litre

= 0.278 M or 278 mM (millimolar)

25Glucose = solute; water = solvent; final = solution

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WATER and pH

H

HO H

HO H

HO H

HO+ +

about 1 in 500 million or 1 in 5 x 108

H

HO

H

HO

H

HO

H

HO

+

+

Water = 55.5 M

oncen ra on o 3 = . x

= 1.11 x 10-7 M ~ 10-7 M = [H3O+] or [H+]

pH = - log10[H+

] = - log10[10-7

] = - (-7) log1010

pH of pure water = 7

(Definition)

26This apparently TINY flexibility has enormous consequences!

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Acetic acid: a weak acid CH3-COOH

HH

O OH

H+

HO

H O

H

H O

but acetic acid holds on to the H more loosely than water thus it is not

1 in 500 million that it will lose the H, but at a much higher frequency

CH3-COOH H+CH3-COO +

1

k2

k1 k2

Forward rate = k1 [CH3-COOH]

Backward rate = +k [CH -COO ] [H ]

At equilibrium: forward rate = backward rate

+

27

1 3 2 3

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- = +-

=Ka =k1

k -

[CH3-COO ]+[H ]

When 50% of the acetic acid ionized,

[CH3-COOH] [CH3-COO ]=i.e. Ka =+[H ]and

a ace c ac = . x

log(ab) = log(a) + log(b)At 50% ionization, = 1.74 x 10-5 M+[H ]

loga(a) = 1

loga

(1) = 0

= log10 (1.74) log10 (10

-5

)

pH = log10 = log10 (1.74 x 10-5)+[H ]

= 0.24 ( 5) = 5 0.24 = 4.76

28

a , a .

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When this equation is generalized to the weak acid HA

=Ka =k1

k2 [CH -COOH]

[CH3-COO ]+[H ]

[A ] +[H ]a [HA]

+[A ]

a

[HA]

pH = - log [H+]

H = K + log

[A ]

29

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Titration curves o ammonia

pKa = 9.3

Titration curves of formic acid

pKa = 3.9

30

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Some common weak acids

31

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Strong acid completely dissociates in water

. .

a solution of hydrogen chloride (gas) in water

HCl H + Cl+

= =+

1 M HCl in water gives 1 M [H ] and 1 M [Cl ]+

10

1 mM HCl ive 0.001 M H+

pH = log10(0.001)

= log10(103)

= 3 lo 10 = 3

32

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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hydrogen Ion

Acidic0

oncen ra on p a ue xamp es o o u ons

100

10

102

103

1

2

Hydrochloric acid

Stomach acid, lemon juice

104

1054

5

Tomatoes

Black coffee

106

Urine107

8

6 Pure water

109 Baking soda

1010

9

10 Great Salt Lake1011 Household ammonia

1012

11

12Household bleach

33Basic1014

13

14 Sodium hydroxide

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Blood pH Symptoms Possible causes

.

7.7

alkalosis

agitated

OD on antacids

7.6

7.5

dizziness

extreme anxiety

7.4 normal range

7.3

7.2 disoriented

kidney disease

7.1 fatigue

severe vomiting

34

.

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4 major classes of macromolecules

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Cellular Structure Polymer Monomer

j

Carbohydrate

CH2OH

H

HO OH

HO

Carbohydrates

Starch grains in a chloroplast Starch Monosaccharide

P

P

TP

T

P

Nitrogenous base

H OH

NucleicAcid

P

PP

P

P

P

G

C

A

A

T C

P

A

P

P

P

C

A

P 5-carbon sugarPhosphate

group

pO

OH

Nucleic acids

Chromosome DNA strand Nucleotide

H CH3

Protein

Intermediate filament Polypeptide Amino acid

AlaAla

Val

Val

SelH

N C C OH

H O

ro e ns

O H H H H H H H H H H H

36

Lipid

Adipose cell with fat droplets Triglyceride Fatty acid

HO

H H H H H H H H H H H

HC C C C C C C C C C C C

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37

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Basic structure of an amino acid

RO H

N C C

H

X-NH2X-NH3

++

+H X-COOH+

+HX-COO

HH

pKa ~ 8.5 pKa ~ 2.5

This structure does not exist !

RO H

H+

RO

H RO

H+

protonated

HO

N C C

H

H

HO

N C C

H HO

N C C

H

H

pH < 2.5pH > 8.5zwitter ion

neutral pH

38

Amino Acids (I)

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( )

A V L I F

N Q Y

G S T

39

Amino Acids (II) 12

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Amino Acids (II)

10.212

4.74.7 6.5

E D H K R

P M C

40

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Nonpolar Glycine, Alanine, Valine, Leucine, Isoleucine,

,

Polar Uncharged Serine, Threonine, Asparagine, Glutamine,

Charged Aspartic Acid, Glutamic Acid, Histidine, Cysteine,

,

Special Function Proline, Methionine, Cysteine

Ionizable Tyrosine, Serine, Threonine

, ,

Disulphide Cysteine (Cystine)

41

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Please note that some amino acids a ear in more than one list

and I have deliberately done so. They are classified as suchdepending on what properties you are talking about. Thus,

tyrosine is polar uncharged, ionizable, and aromatic.

It is often difficult to classify glycine, as it has almost nothing to

. .

Some students query why the uncharged amino acids are known

as such since their amino group and carboxyl groups arecharged at neutral pH. This is because once they are part of a

protein chain, the two groups join together to form a peptide

bond with no charge. The charged uncharged or any other

properties are in reference to the R group only.

If they are free amino acids, then they exist as zwitter ions and

they are charged at the amino and carboxyl groups.

42

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guanidinium

O

imidazole

S

CH2

OH

phenolic

CH2 sulphydryl

No need to memorize

for BS1001/CY1001

cysteine tyroine

43

p ~ . p ~ .

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st nd

Selenocysteine, Sec, U

n a t ree oma ns:

Archaea, bacteria, and eukarya

We have this amino acid in somepro e ns n m nu e quan es.

(a genuine amino acid)

Pyrrolysine, Pyl, OOnly in certain

one bacteria, in enzymes

involved in methane

.

(not universal)

44

Examination nightmare: how many amino acids are there?

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Structural of amino acids

OH R

C C

CN CO

H H

H

mirror images

enantiomers(asymmetric carbon)

Rotation to the right

Cpolarized

lightRotation to the left

45Right and left-handed molecules

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,

In biolo ical s stem we find

only one form or the other.

-

Asymmetric synthesis

of organic molecules

amino acids, but right-handed

nucleic acids and sugars

R

C NCO

H+

HO HE J Corey

1928

46

Nobel Prize in Chemistry

1990

Clock face

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Clock-face

111 12

39

10

567

21 12 11

10

Clock with the heads of prophets

Florence Cathedral, Italy

3

84

9

Note that the clock is counter-clockwise,

a 24 hr clock and starts at the bottom

765

47

end of the clock-face.

Proteins are linear polymers made up of amino acids.

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Proteins are linear polymers made up of amino acids.

CO=

H N3

+

e tide bond Polypeptides: many amino

Add water to break a bond.

Remove water to form a bond.acids joined by peptide bonds.

Proteins: when polypeptides

48

o e n o a unc ona

structure

Carbon bonds

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Carbon bonds

tetrahedral planar linear

1988

H H

Linus Pauling

1901-1994C C N C

O

C C N C

O

+resonance

o e r zes

Chemistry 1954Peace 1962

The peptide bond is planar and not

free to rotate, thus posing a limit of

49

how a polypeptide chain can fold.

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Protein the final active roduct

Polypeptide: a series of amino acids linked together by

e tide bonds also called amide bonds

Primary structure: the sequence of amino acids in the

Higher order structures: different degrees of complex

arrangemen s o e am no ac s n mens ons

Secondary: -helixes, -sheets, turns, and loops

Tertiary: arrangements of the secondary structures into

modules (quite arbitrary)

Quaternary: more than one proteins combine to form a

50

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Any regular features?

= = = = ==

O O O O O O R R R R R R

NCHCNCHCNCHCNCHCNCHCNCHC

HH H H H H

The NH and the C=O can form hydrogen bond.

51

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Right-handed helix

0.54 nm

er a n am no ac s arenot compatible with this

regular structure

52

(pleated) sheet

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-(pleated) sheet

strand

H-bonds between

Certain amino

compatible with

this structure

strand

53

-

These -helices and -sheets are joined together by loops and

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These -helices and -sheets are joined together by loops and

urns, an ey n erac w eac o er, v a e var ous orces, o

form motifs and domains. Quaternary structures are formedwhen the individually folded proteins interact with each other.

54

Fi t 3 d t t f t i l d

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First 3-d structure of a protein solved

-

John KendrewBefore this work, X-ray crystallography was

1917-1997

Nobel Prize

.Proteins are much larger, having thousands

of atoms, instead of 10s. The Nobel Prize

was awarded for the fact that it can be

55

done as much as this is the structure of a

protein, in this case, myoglobin.

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-propeller structure with

7 sheets (blades)

Note that the N-terminal

-strand is the 4th

strandof the 7th blade which

continues to form the 1st

to 4th strand of the 1st

blade (etc) and finally

ends in the 3rd strand ofthe 7th blade.

Note that the N-terminal

and the C-terminal end

up in close proximity

56

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This is known as aRossmann fold with a

central -sheet flanked

by multiple helices. In

this case, the blue

sphere represents adivalent cation (Ca2+ or

Mg2+) which forms part

of the active site of the

structure. This

structure is the ligandbinding domain of the

n egr n su un .

The linear sequence of

- -is mixed

57

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First complex protein structure solved

ax eru z(1914-2002)

Nobel Prize

58

Chemistry 1962

The PSI, hybrid, IEGF-1 domains

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, y ,

o e n egr n su un .

9 disulphide bonds

g ycosy a on s es

Inserted domains:they are formed by

separated linear

segments.

59

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Interactions that contribute to a proteins conformation

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C

CC

O

CH

N

NO

OCC

C

H

H

C C

CH

H

S SC

ON

RC

N

C

H

H

R

O

CO

NH3+

C

CO

ON

N

C

CCH3O

Ionic bondCH3

Disulfide bridge

Hydrogen bond C

CH2

O

N C

van der Waals

attraction

a. b. d.c.

CH3

CH

CH3

CH

CH3

CH3C

H

Hydrophobicexclusion

CH3

CH3C

61

e.

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Forces that hold the protein together

Covalent bonds

Peptide bonds between adjacent amino acids

su p e on s e ween cys e ne res ues

Ionic bonds: between a carboxyl and an amino group

Hydrogen bonds

Hydrophobic interactions: the exclusion of water by

nonpolar regions of the molecules

Van der Waals forces: weak non-covalent attraction at

close range between nonpolar atomsstrength

62

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1/3 bodys protein weight; 75% of skin

Type I : bone, skin, tendons, ligaments, cornea

Type IV : basal lamina (lining blood vessels)

-G-X-Y-G-X-Y-G-X-Y-G-X-Y-G-X-Y-G-X-Y-G-X-Y-G-X-Y-

Every third amino acid is a glycine.

Triple helical structure

63

e a n

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left-handed three

64

helix chains

Can a free polypeptide chain contain necessary

and sufficient information for its folding into a

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functional structure?

Experimentally, can a denatured protein refold?

Christian B.Anfinsen

1916-1995

Nobel Prize

Chemistry

1972

65

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CorrectlHow one type of chaperone protein works

Cap

folded

protein

protein

ADP + P

Chaperone

protein

Chance for protein to refold

66

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Polymorphic proteins: same functions

Phenotype: the observable character

Example: H5N1 or H3N2 of the influenza virus

the influenza virus:

N for Neuraminidase

Target for immune response

67

Variation of proteins sequences

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Species variation:

Haemoglobin

Amino acid variants in the haemoglobin of high altitude birds allow them

, . . .

4 different

am no ac s

Ala / Pro in

-subunit

Bar-headed goose: Winter in India,

May/June in Qinghai-Tibet plateau

Graylag goose: Live in

India all year. Do not

68

.

High affinity haemoglobin.

.

standard affinity.

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Mutant proteins and genetic diseasesDifferent levels of severities

A single amino acid change is sufficient to cause disease

Cannot fold properly

Impaired function

Loss of regulatory capacity

Not all mutations are necessaril deleterious!

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Olympics and Doping

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Building up muscles - steroids

Change the mindset amphetamines

Superior oxygen delivery erythropoeitin (EPO)

to boost the production of red blood cells.

Eero Mntyranta of Finland (1937-), truncated mutation in the EPO receptor,

.

Thus he had, naturally, more red blood cells than other athletes.

3 Olympic gold medals: Squaw Valley 1960 (4 x 10 km Relay) and Innsbruck 1964 (15 km

and 30 km)

2 Olympic silver medals: Innsbruck 1964 (relay) and Grenoble 1968 (15 km)

2 World Championships gold medals: Zakopane 1962 (30 km) and Oslo 1966 (30 km)

2 World Championships silver medals : 1962 (relay) and 1966 (relay)

1 World Championships bronze bronze: 1966 (50 km)

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Mntyranta also finished 19th the 30 km event at the 1972 Winter Olympics in Sapporo

(age 35).

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Fig. 3.18(left middle)

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Fig. 3.18(right 2nd middle)

More Proteins

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Cat Gut (collagen)

73Spider Silk

Keratin based structures

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Beak Feather Hair

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Scale Horn