National Center for
1LJU: X-Ray Structure Of C15a Arsenate Reductase From Pi258 Complexed With Arsenite
All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade
Proc. Natl. Acad. Sci. U. S. A. (2002) 99 p.8506-8511
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.