copper in proteins and enzymes

04/13/2023 Sakharkar Mohammad Anzar 1

Copper Containing Proteins And Enzymes

Presented By:Sakharkar Mohammad AnzarSEM-IIIMSc-II (2013-2014)Inorganic Chemistry (Paper-II)Ramniranjan Jhunjhunwala College

04/13/2023 2

Copper Proteins• Copper proteins are proteins that

contain one or more copper ions

as prosthetic groups.

• The human body contains about 100‐150 mg

of copper.

• The recommended daily dose is about 1‐3

mg/day

• Copper exists as Cu+and Cu2+ionsSakharkar Mohammad Anzar


Copper deficiency

•Anemia

•Steatohepatitis

•Inflammation of the liver

Copper poisoning

•Germicidal effect

•Wilson’s disease


Type-I (Plastocyanin)• Plastocyanin is a copper-containing protein involved in electron-transfer.

• The protein is monomeric, with a molecular weight around 10,500 Daltons, and 99 amino acids in most vascular plants.

• Function:– In photosynthesis, plastocyanin functions as an electron transfer agent between cyto-f of the cyto-b6f complex from P.S- II and P700+ from P.S-I.


• Structure:– The copper binding site is described as a distorted trigonal pyramidal.

– The trigonal plane of the pyramidal base is composed of two nitrogen atoms (N1 and N2) from separate histidines and a sulfur (S1) from a cysteine.

– Sulfur (S2) from an axial methionine forms the apex.

– The ‘distortion’ occurs in the bond lengths between the copper and sulfur ligands.


• Reactions:– Plastocyanin (Cu2+Pc) is reduced by cytochrome f according to the following reaction:

Cu2+Pc + e- → Cu+Pc– After dissociation, Cu+Pc diffuses through the lumen, according to the following reaction:

Cu+Pc → Cu2+Pc + e-– The redox potential is about 370 mV and the isoelectric pH is about 4.


Type II (Amineoxidase)• Copper-containing AO act as a disulphide-linked homodimer. They catalyze the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor:

RCH2NH2 + H2O + O2 RCHO + NH3 + H2O2

• Function:– In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signaling as well as functioning as a vascular adhesion in some mammalian tissues.


• Structure:– The copper amine oxidase 3-dimensional structure was determined through X-ray crystallography.

– The copper amine oxidases occur as mushroom-shaped homodimers of 70-95 kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ)

– The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis.


Type III (Hemocyanin)

• Hemocyanins are proteins that transport oxygen throughout the bodies of some invertebrate animals. These metalloproteins contain two copper atoms that reversibly bind a single oxygen molecule (O2).

• Catalytic activity:– Hemocyanin is homologous to the phenol oxidases since both enzymes sharing type 3 Cu active site coordination.

– Hemocyanin also exhibits phenol oxidase activity, but with slowed kinetics from greater steric bulk at the active site.


• Antitumor effects:– The hemocyanin found in concholepas concholepas blood has immunotherapeutic effects against bladder and prostate cancer

– Mice treated with c. Concholepas showed significant antitumor effects: prolonged survival, decreased tumor growth and incidence, and lack of toxic effects


Cu(A) Type: Cyto. c oxidase• Cytochrome c oxidase is a large transmembrane protein complex found in bacteria and the mitochondrion.

• It is the last enzyme in the respiratory electron transport chain of mitochondria (or bacteria) located in the mitochondrial (or bacterial) membrane.

• It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water.


• Histochemistry : – COX histochemistry is used for mapping regional brain metabolism in animals, since there is a direct relation between enzyme activity and neuronal activity.

– Such brain mapping has been accomplished in spontaneous mutant mice with cerebellar disease such as reeler. and a transgenic model of Alzheimer's disease.

– This technique has also been used to map learning activity in animal brain.


• Genetic defects and disorders:– Defects involving genetic mutations altering cytochrome c oxidase (COX) functionality or structure can result in severe, often fatal metabolic disorders.

– Such disorders usually manifest in early childhood and affect predominantly tissues with high energy demands (brain, heart, muscle).

– Among the many classified mitochondrial diseases, those involving dysfunctional COX assembly are thought to be the most severe.


Copper Enzymes• Copper is an essential element in many of the enzymes that cause oxidations in plants and animals.

• These enzymes are responsible for such varied functions as producing the darkening in cut apple slices, turning green tea into black tea, destroying vitamin C in stored foods.


• The copper probably takes the oxygen from the air, holds it, and then places it on the oxidizable organic substrate.

• However, no stable compound of copper are known that wil hold oxygen.

• Very likely the copper has different properties when chelated by an enzyme than does free copper ion in solution.

• The chemistry of chelated copper is not necessarily the same as the familiar chemistry of copper in solution.


Some examples of Cu-Enzymes

Superoxide dismutase

Tyrosinase

Catechol oxidase


Superoxide dismutase• Superoxide dismutases are enzymes that catalyze the dismutation of superoxide (O2−) into oxygen and hydrogen peroxide. Thus, they are an important antioxidant defense in nearly all cells exposed to oxygen.

Reaction• The SOD-catalysed dismutation of superoxide may be written with the following half-reactions :

• M(n+1)+-SOD + O2− → Mn+-SOD + O2• Mn+-SOD + O2− + 2H+ → M(n+1)+-SOD + H2O2.• where M= Cu (n=1); Mn (n=2); Fe (n=2); Ni (n=2).


• Role in disease:– Overexpression of SOD1 has been linked to the neural disorders seen in down syndrome.

– The extracellular superoxide dismutase (sod3, ecsod) is critical in the development of hypertension.

– Diminished sod3 activity was linked to lung diseases such as acute respiratory distress syndrome (ards) or chronic obstructive pulmonary disease (copd).

• Pharmacological activity: – Sod has powerful antinflammatory activity.– An sod-mimetic agent, tempol, is currently in clinical trials for radioprotection and to prevent radiation-induced hair-loss.


• Cosmetic uses:– SOD may reduce free radical damage to skin—for example, to reduce fibrosis following radiation for breast cancer.

– Superoxide dismutase is known to reverse fibrosis, perhaps through reversion of myofibroblasts back to fibroblasts.


Tyrosinase• Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation, as in the blackening of a peeled potato exposed to air.

• Tyrosinase is an rate limiting enzyme for controlling the production of melanin.

• It is mainly involved in two distinct reactions of melanin synthesis; firstly, the hydroxylation of a monophenol and secondly, the conversion of an O-diphenol to the corresponding O-quinone.


• O-Quinone undergoes several reactions to eventually form melanin.

• It is found inside melanosomes.

• The catalytic action:– of this enzyme is the conversion of tyrosine + O2 to dihydroxyphenylalanine (DOPA), which is then converted to dopaquinone + H2O.

– Dopaquinone in turn, can be readily converted to dopachrome, an orange-red pigment.

– Dopachrome can then be converted to the black/brown melanin pigments .


• Active site:

• The two copper atoms within the active site of tyrosinase enzymes interact with dioxygen to form a highly reactive chemical intermediate that then oxidizes the substrate.

• Tyrosinases and catechol oxidases are collectively termed polyphenol oxidases.


• Transmembrane protein and sorting:

• Human tyrosinase is a single membrane spanning transmembrane protein.

• In humans, tyrosinase is sorted into melanosomes. and the catalytically active domain of the protein resides within melanosomes.

• Only a small enzymatically non-essential part of the protein extends into the cytoplasm of the melanocyte.


Bibliography/Webliography

• Concepts and Models in Bioinorganic Chemistry-

Kraatz, Heinz-Bernhard, & Metzler-Nolte, Nils; • http://www.chem.tamu.edu/rgroup/marcetta/chem489/Pr

esentations/Copper.pdf• http://www.chemwiki.com

http://www.chem.tamu.edu/rgroup/marcetta/chem489/Presentations/Copper.pdf

http://www.chem.tamu.edu/rgroup/marcetta/chem489/Presentations/Copper.pdf

http://www.chemwiki.com/

http://www.chemwiki.com/

copper in proteins and enzymes

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