Structure of Coenzyme A-Disulfide Reductase from Staphylococcus aureus at 1.54 Angstrom Resolution
Coenzyme A (CoASH) replaces glutathione as the major low molecular weight thiol in Staphylococcus aureus; it is maintained in the reduced state by coenzyme A-disulfide reductase (CoADR), a homodimeric enzyme similar to NADH peroxidase but containing a novel Cys43-SSCoA redox center. The crystal structure of S. aureus CoADR has been solved using multiwavelength anomalous dispersion data and refined at a resolution of 1.54 {angstrom}. The resulting electron density maps define the Cys43-SSCoA disulfide conformation, with Cys43-S{gamma} located at the flavin si face, 3.2 {angstrom} from FAD-C4aF, and the CoAS- moiety lying in an extended conformation within a cleft at the dimer interface. A well-ordered chloride ion is positioned adjacent to the Cys43-SSCoA disulfide and receives a hydrogen bond from Tyr361'-OH of the complementary subunit, suggesting a role for Tyr361' as an acid-base catalyst during the reduction of CoAS-disulfide. Tyr419'-OH is located 3.2 {angstrom} from Tyr361'-OH as well and, based on its conservation in known functional CoADRs, also appears to be important for activity. Identification of residues involved in recognition of the CoAS-disulfide substrate and in formation and stabilization of the Cys43-SSCoA redox center has allowed development of a CoAS-binding motif. Bioinformatics analyses indicate that CoADR enzymes are broadly distributed in both bacterial and archaeal kingdoms, suggesting an even broader significance for the CoASH/CoAS-disulfide redox system in prokaryotic thiol/disulfide homeostasis.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 930257
- Report Number(s):
- BNL-80949-2008-JA; TRN: US200822%%1425
- Journal Information:
- Biochemistry, Vol. 45; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
36 MATERIALS SCIENCE
CATALYSTS
CHLORIDES
COENZYMES
CRYSTAL STRUCTURE
DATA
DIMERS
DISPERSIONS
DISULFIDES
ELECTRON DENSITY
ENZYMES
FACE
FUNCTIONALS
GLUTATHIONE
HOMEOSTASIS
HYDROGEN
IONS
ISOALLOXAZINES
MAPS
MOLECULAR WEIGHT
OXIDOREDUCTASES
PEROXIDASES
REDUCTION
RESIDUES
RESOLUTION
STABILIZATION
STAPHYLOCOCCUS
SUBSTRATES
THIOLS
national synchrotron light source