All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.
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Messens J, Martins JC, Van Belle K, Brosens E, Desmyter A, De Gieter M, Wieruszeski JM, Willem R, Wyns L, Zegers I
All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8506-11. Epub 2002 Jun 18.
- PubMed ID
- 12072565 [ View in PubMed]
- 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.