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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1vlb
Original Entry
Title:
Oxidoreductase
Compound:
Aldehyde oxidoreductase
Mutant:
No
UniProt/Swiss-Prot:
Q46509-MOP_DESGI
EC Class:
1.2.99.7
Other CSA Entries:
Overview of all sites for 1vlb
Homologues of 1vlb
Entries for UniProt/Swiss-Prot: Q46509
Entries for EC: 1.2.99.7
Other Databases:
PDB entry: 1vlb
PDBsum entry: 1vlb
UniProt/Swiss-Prot: Q46509
IntEnz entry: 1.2.99.7
Literature Report:
Introduction:
The 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).
Mechanism:
The 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.

Sites:

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Found by:
Literature reference 
PsiBLAST alignment on 1fiq

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
908 0
Electron donor/acceptorCofactor
The [2Fe-2S] clusters transfer electrons from the molybdenum to the external electron acceptor.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8799115 Current protein Ligand is essential for catalysis
PubMed ID 8799115 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
909 0
Electron donor/acceptorCofactor
The [2Fe-2S] clusters transfer electrons from the molybdenum to the external electron acceptor.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8799115 Current protein Ligand is essential for catalysis
PubMed ID 8799115 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
921 0
Substrate
ElectrophileSubstrate
ElectrostaticWater
The molybdenum cofactor (Mo-co) undergoes redox changes during the reaction. The sulfido ligand accepts hydride from the substrate. Since Mo also coordinates the nucleophilic water molecule it may also activate it.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8799115 Current protein Ligand is essential for catalysis
PubMed ID 8799115 Current protein Residue is covalently bound to intermediate, based on structural data
PubMed ID 8799115 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUA 869 869Sidechain
Acid/baseWater
Steric hindranceSubstrate
Glu 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).
Evidence from paper Evidence concerns Evidence type
PubMed ID 8799115 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 8799115 Current protein Residue is covalently bound to intermediate, based on structural data
Notes:

References:
1
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes.
R. Huber and P. Hof and R. O. Duarte and J. J. Moura and I. Moura and M. Y. Liu and J. LeGall and R. Hille and M. Archer and M. J. Romão
Proc Natl Acad Sci U S A 93, (17) 8846-51, (1996).
8799115
2
Molybdenum-cofactor-containing enzymes: structure and mechanism.
C. Kisker and H. Schindelin and D. C. Rees
Annu Rev Biochem 66, () 233-67, (1997).
9242907
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