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3v4n
From Proteopedia
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| - | [[Image:3v4n.jpg|left|200px]] | ||
| - | + | ==The Biochemical and Structural Basis for Inhibition of Enterococcus faecalis HMG-CoA Synthatse, mvaS, by Hymeglusin== | |
| - | + | <StructureSection load='3v4n' size='340' side='right'caption='[[3v4n]], [[Resolution|resolution]] 1.60Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3v4n]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V4N FirstGlance]. <br> | |
| - | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene></td></tr> | |
| - | -- | + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SNC:S-NITROSO-CYSTEINE'>SNC</scene></td></tr> |
| - | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3v4x|3v4x]]</div></td></tr> | |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mvaS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 "Enterococcus proteiformis" Thiercelin and Jouhaud 1903])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_synthase Hydroxymethylglutaryl-CoA synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.10 2.3.3.10] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v4n OCA], [https://pdbe.org/3v4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v4n RCSB], [https://www.ebi.ac.uk/pdbsum/3v4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v4n ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Hymeglusin (1233A, F244, L-659-699) is established as a specific beta-lactone inhibitor of eukaryotic hydroxymethylglutaryl-CoA synthase (HMGCS). Inhibition results from formation of a thioester adduct to the active site cysteine. In contrast, the effects of hymeglusin on bacterial HMG-CoA synthase, mvaS, have been minimally characterized. Hymeglusin blocks growth of Enterococcus faecalis. After removal of the inhibitor from culture media, a growth curve inflection point at 3.1 h is observed (vs 0.7 h for the uninhibited control). Upon hymeglusin inactivation of purified E. faecalis mvaS, the thioester adduct is more stable than that measured for human HMGCS. Hydroxylamine cleaves the thioester adduct; substantial enzyme activity is restored at a rate that is 8-fold faster for human HMGCS than for mvaS. Structural results explain these differences in enzyme-inhibitor thioester adduct stability and solvent accessibility. The E. faecalis mvaS-hymeglusin cocrystal structure (1.95 A) reveals virtually complete occlusion of the bound inhibitor in a narrow tunnel that is largely sequestered from bulk solvent. In contrast, eukaryotic (Brassica juncea) HMGCS binds hymeglusin in a more solvent-exposed cavity. | ||
| - | + | Biochemical and structural basis for inhibition of Enterococcus faecalis hydroxymethylglutaryl-CoA synthase, mvaS, by hymeglusin.,Skaff DA, Ramyar KX, McWhorter WJ, Barta ML, Geisbrecht BV, Miziorko HM Biochemistry. 2012 Jun 12;51(23):4713-22. doi: 10.1021/bi300037k. Epub 2012 May, 25. PMID:22510038<ref>PMID:22510038</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | == | + | </div> |
| - | + | <div class="pdbe-citations 3v4n" style="background-color:#fffaf0;"></div> | |
| - | [[Category: Enterococcus | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]] | ||
[[Category: Hydroxymethylglutaryl-CoA synthase]] | [[Category: Hydroxymethylglutaryl-CoA synthase]] | ||
| - | [[Category: Geisbrecht, B V | + | [[Category: Large Structures]] |
| - | [[Category: McWhorter, W J | + | [[Category: Geisbrecht, B V]] |
| - | [[Category: Miziorko, H M | + | [[Category: McWhorter, W J]] |
| - | [[Category: Ramyar, K X | + | [[Category: Miziorko, H M]] |
| - | [[Category: Skaff, D A | + | [[Category: Ramyar, K X]] |
| + | [[Category: Skaff, D A]] | ||
[[Category: Hydroxymethylglutaryl-coa synthase]] | [[Category: Hydroxymethylglutaryl-coa synthase]] | ||
[[Category: Nitrosylation]] | [[Category: Nitrosylation]] | ||
[[Category: Transferase-inhibitor complex]] | [[Category: Transferase-inhibitor complex]] | ||
Current revision
The Biochemical and Structural Basis for Inhibition of Enterococcus faecalis HMG-CoA Synthatse, mvaS, by Hymeglusin
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