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Title: Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus: SauMacro/SAV0325 X-Ray Structure

Authors:
 [1];  [1];  [1];  [1]
  1. Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, US National Institutes of Health, Department of Health and Human Services, Research Triangle Park North Carolina 27709
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1314253
Resource Type:
Journal Article
Resource Relation:
Journal Name: Protein Science; Journal Volume: 25; Journal Issue: 9
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Appel, C. Denise, Feld, Geoffrey K., Wallace, Bret D., and Williams, R. Scott. Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus: SauMacro/SAV0325 X-Ray Structure. United States: N. p., 2016. Web. doi:10.1002/pro.2974.
Appel, C. Denise, Feld, Geoffrey K., Wallace, Bret D., & Williams, R. Scott. Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus: SauMacro/SAV0325 X-Ray Structure. United States. doi:10.1002/pro.2974.
Appel, C. Denise, Feld, Geoffrey K., Wallace, Bret D., and Williams, R. Scott. 2016. "Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus: SauMacro/SAV0325 X-Ray Structure". United States. doi:10.1002/pro.2974.
@article{osti_1314253,
title = {Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus: SauMacro/SAV0325 X-Ray Structure},
author = {Appel, C. Denise and Feld, Geoffrey K. and Wallace, Bret D. and Williams, R. Scott},
abstractNote = {},
doi = {10.1002/pro.2974},
journal = {Protein Science},
number = 9,
volume = 25,
place = {United States},
year = 2016,
month = 7
}
  • No abstract prepared.
  • No abstract prepared.
  • The dimeric repressor MecI regulates the mecA gene that encodes the penicillin-binding protein PBP-2a in methicillin-resistant Staphylococcus aureus (MRSA). MecI is similar to BlaI, the repressor for the blaZ gene of {beta}-lactamase. MecI and BlaI can bind to both operator DNA sequences. The crystal structure of MecI in complex with the 32 base-pair cognate DNA of mec was determined to 3.8 Angstroms resolution. MecI is a homodimer and each monomer consists of a compact N-terminal winged-helix domain, which binds to DNA, and a loosely packed C-terminal helical domain, which intertwines with its counter-monomer. The crystal contains horizontal layers of virtualmore » DNA double helices extending in three directions, which are separated by perpendicular DNA segments. Each DNA segment is bound to two MecI dimers. Similar to the BlaI-mec complex, but unlike the MecI-bla complex, the MecI repressors bind to both sides of the mec DNA dyad that contains four conserved sequences of TACA/TGTA. The results confirm the up-and-down binding to the mec operator, which may account for cooperative effect of the repressor.« less
  • 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 themore » 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.« less