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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1vlb

E.C. namealdehyde dehydrogenase (FAD-independent)
SpeciesDesulfovibrio gigas (Bacteria)
E.C. Number (IntEnz) 1.2.99.7
CSA Homologues of 1vlb
CSA Entries With UniProtID Q46509
CSA Entries With EC Number 1.2.99.7
PDBe Entry 1vlb
PDBSum Entry 1vlb
MACiE Entry M0105

Literature Report

IntroductionThe sulfate-reducing bacteria Desulfovibrio gigas synthesises a xanthine oxidase-related molybdenum-iron protein aldehyde oxidoreductase (Mop) which catalyses the oxidation of aldehydes to carboxylic acids. Mop contains two separate [2Fe-2S] clusters, and an Mo ion held by a pterin derivative called molybdopterin cytosine dinucleotide (together called the molybedenum cofactor, Mo-co).
MechansimThe general reaction is attack of hydroxide on the aldehyde, while the terminal aldehyde hydride is transferred to the sulfido ligand of Mo.
1) In the resting enzyme, moldybdenum is Mo(VI) and coordinated to molybdopterin and water, with oxo and sulfido ligands.
2) Glu 869 deprotonates the coordinated water as it attacks, as hydroxide, the electrophilic carbonyl. At the same time, the aldehyde delivers hydride to the sulfido ligand. This reduces the Mo=S bond to Mo-S, with Mo(IV) reduced to Mo(VI). The carboxylic acid product is bound to Mo(VI).
3) Glu 869 coordinates to Mo(IV), with the carboxylic proton being transferred to a general base (another water molecule) and the carboxylic acid product being released from Mo(IV).
4) An electron is transferred from Mo(IV) to one of the iron-sulphur clusters. Mo(IV) is thus oxidised to Mo(V).
5) A second electron is transferred from Mo(V) to one of the iron-sulphur clusters. Mo(V) is thus oxidised to Mo(VI), with the sulfide proton being removed by a general base (a third water molecule) and the Mo=S bond regenerated.
The Mo oxidation steps are not fully known in terms of which iron-sulphur cluster atoms accept and pass on electrons. Ultimately, the electrons from the reduced iron-sulphur clusters are passed to an external acceptor. Mop is able to form part of electron transfer chains together with flavoredoxin. However, Mop does not bind a flavin cofactor, unlike its relative xanthine oxidase.
Reaction

Catalytic Sites for 1vlb

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA869869macie:sideChainGlu 869 acts as a general base, deprotonating the nucleophilic water molecule.
Glu 869 also displaces the product from Mo(IV) by coordinating to Mo(IV).

Literature References

Notes:
Huber R
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes.
Proc Natl Acad Sci U S A 1996 93 8846-8851
PubMed: 8799115
Kisker C
Molybdenum-cofactor-containing enzymes: structure and mechanism.
Annu Rev Biochem 1997 66 233-267
PubMed: 9242907
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