1YQZ

Structure of Coenzyme A-Disulfide Reductase from Staphylococcus aureus refined at 1.54 Angstrom resolution

Summary for 1YQZ

• Entry DOI: 10.2210/pdb1yqz/pdb
• Descriptor: coenzyme A disulfide reductase, MAGNESIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 102091.23

Authors

Mallett, T.C.,Wallen, J.R.,Sakai, H.,Luba, J.,Parsonage, D.,Karplus, P.A.,Tsukihara, T.,Claiborne, A. (deposition date: 2005-02-02, release date: 2006-05-09, Last modification date: 2024-11-20)

Primary citation

Mallett, T.C.,Wallen, J.R.,Karplus, P.A.,Sakai, H.,Tsukihara, T.,Claiborne, A.
Structure of coenzyme A-disulfide reductase from Staphylococcus aureus at 1.54 A resolution.
Biochemistry, 45:11278-11289, 2006

PubMed Abstract: 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 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.

PubMed: 16981688
DOI: 10.1021/bi061139a

Experimental method

X-RAY DIFFRACTION (1.54 Å)