Title | All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade. |
Publication Type | Journal Article |
Year of Publication | 2002 |
Authors | Messens, J., J. C. Martins, K. Van Belle, E. Brosens, A. Desmyter, M. De Gieter, J-M. Wieruszeski, R. Willem, L. Wyns, and I. Zegers |
Journal | Proc Natl Acad Sci U S A |
Volume | 99 |
Issue | 13 |
Pagination | 8506-11 |
Date Published | 2002 Jun 25 |
ISSN | 0027-8424 |
Keywords | Arsenates, Arsenite Transporting ATPases, Catalysis, Gram-Positive Bacteria, Ion Pumps, Kinetics, Models, Molecular, Multienzyme Complexes, Mutagenesis, Site-Directed, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Sulfhydryl Compounds |
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. |
DOI | 10.1073/pnas.132142799 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 12072565 |
PubMed Central ID | PMC124290 |
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