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Structure of Coenzyme A-Disulfide Reductase from Staphylococcus aureus refined at 1.54 Angstrom resolution
Structural highlights
FunctionCDR_STAA8 Catalyzes specifically the NADPH-dependent reduction of coenzyme A disulfide. Is also active with other disulfide substrates containing at least one 4'-phosphopantethienyl moiety such as 4,4'-diphosphopantethine, but is not able to reduce oxidized glutathione, cystine, pantethine, or H(2)O(2).[HAMAP-Rule:MF_01608] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCoenzyme 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 A. The resulting electron density maps define the Cys43-SSCoA disulfide conformation, with Cys43-S(gamma) located at the flavin si face, 3.2 A 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 A 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. Structure of coenzyme A-disulfide reductase from Staphylococcus aureus at 1.54 A resolution.,Mallett TC, Wallen JR, Karplus PA, Sakai H, Tsukihara T, Claiborne A Biochemistry. 2006 Sep 26;45(38):11278-89. PMID:16981688[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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