4eqr: Difference between revisions
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==Crystal structure of the Y361F mutant of Staphylococcus aureus CoADR== | ==Crystal structure of the Y361F mutant of Staphylococcus aureus CoADR== | ||
<StructureSection load='4eqr' size='340' side='right' caption='[[4eqr]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='4eqr' size='340' side='right' caption='[[4eqr]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4eqr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4eqr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Staa3 Staa3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EQR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EQR FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yqz|1yqz]], [[4em3|4em3]], [[4em4|4em4]], [[4emw|4emw]], [[4eqs|4eqs]], [[4eqw|4eqw]], [[4eqx|4eqx]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yqz|1yqz]], [[4em3|4em3]], [[4em4|4em4]], [[4emw|4emw]], [[4eqs|4eqs]], [[4eqw|4eqw]], [[4eqx|4eqx]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cdr, SAUSA300_0873 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=367830 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cdr, SAUSA300_0873 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=367830 STAA3])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/CoA-disulfide_reductase CoA-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.14 1.8.1.14] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/CoA-disulfide_reductase CoA-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.14 1.8.1.14] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eqr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eqr RCSB], [http://www.ebi.ac.uk/pdbsum/4eqr PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eqr OCA], [http://pdbe.org/4eqr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eqr RCSB], [http://www.ebi.ac.uk/pdbsum/4eqr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eqr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4eqr" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: CoA-disulfide reductase]] | [[Category: CoA-disulfide reductase]] | ||
[[Category: | [[Category: Staa3]] | ||
[[Category: Claiborne, A]] | [[Category: Claiborne, A]] | ||
[[Category: Edwards, J S]] | [[Category: Edwards, J S]] | ||
Revision as of 03:37, 5 August 2016
Crystal structure of the Y361F mutant of Staphylococcus aureus CoADRCrystal structure of the Y361F mutant of Staphylococcus aureus CoADR
Structural highlights
Function[CDR_STAA3] Catalyzes specifically the NADPH-dependent reduction of coenzyme A disulfide.[HAMAP-Rule:MF_01608] Publication Abstract from PubMedDisruption of the unusual thiol-based redox homeostasis mechanisms in Staphylococcus aureus represents a unique opportunity to identify new metabolic processes and new targets for intervention. Targeting uncommon aspects of CoASH biosynthetic and redox functions in S. aureus, the antibiotic CJ-15,801 has recently been demonstrated to be an antimetabolite of the CoASH biosynthetic pathway in this organism; CoAS-mimetics containing alpha,beta-unsaturated sulfone and carboxyl moieties have also been exploited as irreversible inhibitors of S. aureus coenzyme A-disulfide reductase (SaCoADR). In this work we have determined the crystal structures of three of these covalent SaCoADR-inhibitor complexes, prepared by inactivation of wild-type enzyme during turnover. The structures reveal the covalent linkage between the active-site Cys43-S(gamma) and C(beta) of the vinyl sulfone or carboxyl moiety. The full occupancy of two inhibitor molecules per enzyme dimer, together with kinetic analyses of the wild-type/C43S heterodimer, indicates that half-sites-reactivity is not a factor during normal catalytic turnover. Further, we provide the structures of SaCoADR active-site mutants; in particular, Tyr419'-OH plays dramatic roles in directing intramolecular reduction of the Cys43-SSCoA redox center, in the redox asymmetry observed for the two FAD per dimer in NADPH titrations, and in catalysis. The two conformations observed for the Ser43 side chain in the C43S mutant structure lend support to a conformational switch for Cys43-S(gamma) during its catalytic Cys43-SSCoA/Cys43-SH redox cycle. Finally, the structures of the three inhibitor complexes provide a framework for design of more effective inhibitors with therapeutic potential against several major bacterial pathogens. Turnover-Dependent Covalent Inactivation of Staphylococcus aureus Coenzyme A-Disulfide Reductase by Coenzyme A-Mimetics: Mechanistic and Structural Insights.,Wallace BD, Edwards JS, Wallen JR, Moolman WJ, van der Westhuyzen R, Strauss E, Redinbo MR, Claiborne A Biochemistry. 2012 Oct 2;51(39):7699-711. doi: 10.1021/bi301026c. Epub 2012 Sep, 19. PMID:22954034[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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