3v4x: Difference between revisions

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'''Unreleased structure'''


The entry 3v4x is ON HOLD  until Paper Publication
==The Biochemical and Structural Basis for Inhibition of Enterococcus faecalis HMG-CoA Synthase, mvaS, by Hymeglusin==
<StructureSection load='3v4x' size='340' side='right'caption='[[3v4x]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3v4x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V4X FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.952&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F24:(7R,12R,13R)-13-FORMYL-12,14-DIHYDROXY-3,5,7-TRIMETHYLTETRADECA-2,4-DIENOIC+ACID'>F24</scene></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=3v4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v4x OCA], [https://pdbe.org/3v4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v4x RCSB], [https://www.ebi.ac.uk/pdbsum/3v4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v4x ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HMGCS_ENTFL HMGCS_ENTFL] Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoid compounds.<ref>PMID:12107122</ref> <ref>PMID:23794621</ref>
<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.


Authors: Skaff, D.A., Ramyar, K.X., McWhorter, W.J., Geisbrecht, B.V., Miziorko, H.M.
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>


Description: The Biochemical and Structural Basis for Inhibition of Enterococcus faecalis HMG-CoA Synthase, mvaS, by Hymeglusin
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3v4x" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterococcus faecalis]]
[[Category: Large Structures]]
[[Category: Geisbrecht BV]]
[[Category: McWhorter WJ]]
[[Category: Miziorko HM]]
[[Category: Ramyar KX]]
[[Category: Skaff DA]]
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