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O O + supporting proton acid
RC + H O RC + HZR' H
2
Z R' Z OH 2+ H
Z = O: esterases Zn O
Z = NH: peptidases electrophilic
Z = phosphate: phosphatases attack
protein
nucleophilic attack

-
-
- Others: Carboanhydrase (CO 2 + OH ' HCO 3 ; ch. 3 and Fig. 7)
+
-
Alcoholdehydrogenase (RCH 2OH → RCHO + 2H + 2e ; see below)

Structural: Stabilisation of the tertiary structure of protein domains in enzymes (e.g. Cu,Zn
2+
superoxide dismutase, alcoholdehydrogenase, cytochrome-c oxidase). Here, Zn is
tetrahedrally coordinated by four amino acid residues.

Stabilisation of quaternary structures, e.g. of the hexameric storage form of the peptide
2+
hormone insulin, where the monomers are linked by [Zn(His) 3(H 2O) 3] .

Zinc finger are constituents of numerous genetic transcription factors. Coordination mode
typically is [Zn(Cys) 2(His) 2].

Ada repair protein: Repairs (by de-methylation) O Base
methylated phosphate linkers in DNA by transfer of the S
2+
methyl group to cysteinate coordinated to Zn . O O S S
P Zn
2+
Thioneins: Storage of Zn /storage of cysteine; O O CH 3 S
2+
detoxification of Cd and other thiophilic metal ions; mode O Base
2-
of coordination: [Zn(Cys) 4] .

Synaptic transmission: Zinc ions modulate the synaptic
activity of brain cells that use glycine as a neurotransmitter.

Examples for enzymes

(for carbonic anhydrase, see ch. 3 )

Carboxypeptidase A (from bovine pancreas), is an exo-peptidase of molecular weight 36.4
kDa, which breaks down peptides from their C-terminus. The substrate (the peptide) is
activated by coordination of the carbonyl oxygen of the peptide backbone to the Lewis-acid
2+
Zn centre. For the several steps of the enzymatic reaction see Fig. 25.

Alcoholdehydrogenase is a homodimer of molecular weight 80 kDa, which catalyses the
following reaction:
+
RCH 2OH + NAD → RCHO + NADH 2
The cofactor NAD is bound by salt interaction and hydrogen bridges close to the active centre.
2+
2+
Each subunit contains a catalytically active Zn (Cys, H 2O, two His) and a structural Zn
centre (four Cys). The mechanism of alcohol dehydrogenation is sketched in Fig. 26: The
-
2+
alcohol is bound to and thus activated by Zn , and deprotonated by the neighbouring OH . The
+
alkoxido ligand thus generated then transfers a hydride to the cofactor NAD , and the carbo-
cation gets stabilised by formation of the aldehyde.