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All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.

ABSTRACT: The mechanism of pI258 arsenate reductase (ArsC) catalyzed arsenate reduction, involving its P-loop structural motif and three redox active cysteines, has been unraveled. All essential intermediates are visualized with x-ray crystallography, and NMR is used to map dynamic regions in a key disulfide intermediate. Steady-state kinetics of ArsC mutants gives a view of the crucial residues for catalysis. ArsC combines a phosphatase-like nucleophilic displacement reaction with a unique intramolecular disulfide bond cascade. Within this cascade, the formation of a disulfide bond triggers a reversible "conformational switch" that transfers the oxidative equivalents to the surface of the protein, while releasing the reduced substrate.

SUBMITTER: Messens J

PROVIDER: S-EPMC124290 | biostudies-literature | 2002 Jun

REPOSITORIES: biostudies-literature

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All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.

Messens Joris J Martins José C JC Van Belle Karolien K Brosens Elke E Desmyter Aline A De Gieter Marjan M Wieruszeski Jean-Michel JM Willem Rudolph R Wyns Lode L Zegers Ingrid I

Proceedings of the National Academy of Sciences of the United States of America 20020618 13

The mechanism of pI258 arsenate reductase (ArsC) catalyzed arsenate reduction, involving its P-loop structural motif and three redox active cysteines, has been unraveled. All essential intermediates are visualized with x-ray crystallography, and NMR is used to map dynamic regions in a key disulfide intermediate. Steady-state kinetics of ArsC mutants gives a view of the crucial residues for catalysis. ArsC combines a phosphatase-like nucleophilic displacement reaction with a unique intramolecular ...[more]

PMID: 12072565

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