The molybdenum site in the xanthine oxidase-related aldehyde oxidoreductase from Desulfovibrio gigas and a catalytic mechanism for this class of enzymes

Maria João Romão, Notker Rösch, Robert Huber

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

The crystal structure analysis of the aldehyde oxidoreductase from Desulfovibrio gigas was exceptionally revealing with regard to the ligands and structure of the molybdenum site and the mechanism of the hydroxylation reaction catalyzed. The metal is pentacoordinated by two sulfurs of the cis- dithiolene group of the molybdopterin cofactor and by facially arranged sulfido, oxo and water ligands. The latter is in hydrogen-bonding contact with the carboxylate group of Glu 869 and the hydroxyl group of an isopropanol molecule, a substrate analogue inhibitor. This steric arrangement strongly suggests a mechanism for the reductive half-cycle of the reaction with Glu 869 as the base, the metal-bound water as the source of the transferred hydroxyl group, and the sulfido group as the hydride acceptor. The geometry and the proposed mechanism are in agreement with density functional calculations on a model of the molybdenum site. In the oxidative half-reaction, electrons are withdrawn from Mo(IV) through the rigidly held pterin ring system, via the iron-sulfur clusters, to the protein surface.

Original languageEnglish
Pages (from-to)782-785
Number of pages4
JournalJournal of Biological Inorganic Chemistry
Volume2
Issue number6
DOIs
Publication statusPublished - 1 Dec 1997

Fingerprint

Aldehyde Oxidoreductases
Desulfovibrio gigas
Molybdenum
Xanthine Oxidase
Sulfur
Hydroxyl Radical
Metals
Pterins
Ligands
Hydroxylation
2-Propanol
Water
Enzymes
Hydrogen Bonding
Hydrides
Density functional theory
Hydrogen bonds
Membrane Proteins
Iron
Crystal structure

Keywords

  • Molybdoenzymes
  • Molybdopterin
  • Protein crystallography
  • Xanthine oxidase

Cite this

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title = "The molybdenum site in the xanthine oxidase-related aldehyde oxidoreductase from Desulfovibrio gigas and a catalytic mechanism for this class of enzymes",
abstract = "The crystal structure analysis of the aldehyde oxidoreductase from Desulfovibrio gigas was exceptionally revealing with regard to the ligands and structure of the molybdenum site and the mechanism of the hydroxylation reaction catalyzed. The metal is pentacoordinated by two sulfurs of the cis- dithiolene group of the molybdopterin cofactor and by facially arranged sulfido, oxo and water ligands. The latter is in hydrogen-bonding contact with the carboxylate group of Glu 869 and the hydroxyl group of an isopropanol molecule, a substrate analogue inhibitor. This steric arrangement strongly suggests a mechanism for the reductive half-cycle of the reaction with Glu 869 as the base, the metal-bound water as the source of the transferred hydroxyl group, and the sulfido group as the hydride acceptor. The geometry and the proposed mechanism are in agreement with density functional calculations on a model of the molybdenum site. In the oxidative half-reaction, electrons are withdrawn from Mo(IV) through the rigidly held pterin ring system, via the iron-sulfur clusters, to the protein surface.",
keywords = "Molybdoenzymes, Molybdopterin, Protein crystallography, Xanthine oxidase",
author = "Rom{\~a}o, {Maria Jo{\~a}o} and Notker R{\"o}sch and Robert Huber",
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TY - JOUR

T1 - The molybdenum site in the xanthine oxidase-related aldehyde oxidoreductase from Desulfovibrio gigas and a catalytic mechanism for this class of enzymes

AU - Romão, Maria João

AU - Rösch, Notker

AU - Huber, Robert

PY - 1997/12/1

Y1 - 1997/12/1

N2 - The crystal structure analysis of the aldehyde oxidoreductase from Desulfovibrio gigas was exceptionally revealing with regard to the ligands and structure of the molybdenum site and the mechanism of the hydroxylation reaction catalyzed. The metal is pentacoordinated by two sulfurs of the cis- dithiolene group of the molybdopterin cofactor and by facially arranged sulfido, oxo and water ligands. The latter is in hydrogen-bonding contact with the carboxylate group of Glu 869 and the hydroxyl group of an isopropanol molecule, a substrate analogue inhibitor. This steric arrangement strongly suggests a mechanism for the reductive half-cycle of the reaction with Glu 869 as the base, the metal-bound water as the source of the transferred hydroxyl group, and the sulfido group as the hydride acceptor. The geometry and the proposed mechanism are in agreement with density functional calculations on a model of the molybdenum site. In the oxidative half-reaction, electrons are withdrawn from Mo(IV) through the rigidly held pterin ring system, via the iron-sulfur clusters, to the protein surface.

AB - The crystal structure analysis of the aldehyde oxidoreductase from Desulfovibrio gigas was exceptionally revealing with regard to the ligands and structure of the molybdenum site and the mechanism of the hydroxylation reaction catalyzed. The metal is pentacoordinated by two sulfurs of the cis- dithiolene group of the molybdopterin cofactor and by facially arranged sulfido, oxo and water ligands. The latter is in hydrogen-bonding contact with the carboxylate group of Glu 869 and the hydroxyl group of an isopropanol molecule, a substrate analogue inhibitor. This steric arrangement strongly suggests a mechanism for the reductive half-cycle of the reaction with Glu 869 as the base, the metal-bound water as the source of the transferred hydroxyl group, and the sulfido group as the hydride acceptor. The geometry and the proposed mechanism are in agreement with density functional calculations on a model of the molybdenum site. In the oxidative half-reaction, electrons are withdrawn from Mo(IV) through the rigidly held pterin ring system, via the iron-sulfur clusters, to the protein surface.

KW - Molybdoenzymes

KW - Molybdopterin

KW - Protein crystallography

KW - Xanthine oxidase

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U2 - 10.1007/s007750050195

DO - 10.1007/s007750050195

M3 - Review article

VL - 2

SP - 782

EP - 785

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 1432-1327

IS - 6

ER -