Alcohol dehydrogenase (class V)
To date, all known attempts to isolate and characterize mammalian class V alcohol dehydrogenase, a member of the large zinc-dependent ADH protein family, at the protein level have failed. Suggesting that the class V ADH protein is not stable in a non-cellular environment (unlike most other ADH proteins). Members of this protein family are all involved in the general metabolism of alcohols and aldehydes.
Reference Protein
- Sequence
-
P28332
(1.1.1.1)
(Sequence Homologues)
- Biological species
-
Homo sapiens (Human)
- Cofactors
- Zinc(2+) (2)
Enzyme Reaction (EC:1.1.1.1)
+
→
+
+
Alternative enzyme names: ADH, NAD-dependent alcohol dehydrogenase, NAD-specific aromatic alcohol dehydrogenase, NADH-alcohol dehydrogenase, NADH-aldehyde dehydrogenase, Alcohol dehydrogenase (NAD), Aldehyde reductase, Aliphatic alcohol dehydrogenase, Ethanol dehydrogenase, Primary alcohol dehydrogenase, Yeast alcohol dehydrogenase,
Enzyme Mechanism
Introduction
Specifics of the mechanism are not yet known, save via homology to other zinc-dependent alcohol dehydrogenases. It is likely that Lys52 acts as the general acid/base in the unique catalytic triad.
Catalytic Residues Roles
| UniProt | ||
| Cys102, Cys105, Cys113, Cys99 | Binds the structural zinc ion. | metal ligand |
| Cys47, His69, Cys175 | Binds the catalytic zinc ion. | metal ligand |
| Lys52 | Putative general acid/base | proton shuttle (general acid/base) |
| Met51, Glu50 | Activates Lys52, stabilises reaction intermediates. | modifies pKa, electrostatic stabiliser |
Chemical Components
References
- Östberg LJ et al. (2016), BMC Biochem, 17, 16-. Computational studies of human class V alcohol dehydrogenase - the odd sibling. DOI:10.1186/s12858-016-0072-y. PMID:27455956.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| Cys47 | metal ligand |
| His69 | metal ligand |
| Cys99 | metal ligand |
| Cys102 | metal ligand |
| Cys105 | metal ligand |
| Cys113 | metal ligand |
| Cys175 | metal ligand |
| Glu50 | modifies pKa |
| Met51 | modifies pKa |
| Lys52 | proton shuttle (general acid/base) |
| Glu50 | electrostatic stabiliser |
| Met51 | electrostatic stabiliser |