2wya: Difference between revisions

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-{{Seed}}
-[[Image:2wya.png|left|200px]]
-<!--
+==CRYSTAL STRUCTURE OF HUMAN MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL- COENZYME A SYNTHASE 2 (HMGCS2)==
-The line below this paragraph, containing "STRUCTURE_2wya", creates the "Structure Box" on the page.
+<StructureSection load='2wya' size='340' side='right'caption='[[2wya]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2wya]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2v4w 2v4w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WYA FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HMG:3-HYDROXY-3-METHYLGLUTARYL-COENZYME+A'>HMG</scene></td></tr>
-{{STRUCTURE_2wya|  PDB=2wya  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wya OCA], [https://pdbe.org/2wya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wya RCSB], [https://www.ebi.ac.uk/pdbsum/2wya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wya ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/HMCS2_HUMAN HMCS2_HUMAN] 3-hydroxy-3-methylglutaryl-CoA synthase deficiency. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/HMCS2_HUMAN HMCS2_HUMAN] Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate.<ref>PMID:11228257</ref> <ref>PMID:23751782</ref> <ref>PMID:29597274</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wy/2wya_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wya ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+-Hydroxy-3-methylglutaryl coenzyme A (CoA) synthase (HMGCS) catalyzes the condensation of acetyl-CoA and acetoacetyl-CoA into 3-hydroxy-3-methylglutaryl CoA. It is ubiquitous across the phylogenetic tree and is broadly classified into three classes. The prokaryotic isoform is essential in Gram-positive bacteria for isoprenoid synthesis via the mevalonate pathway. The eukaryotic cytosolic isoform also participates in the mevalonate pathway but its end product is cholesterol. Mammals also contain a mitochondrial isoform; its deficiency results in an inherited disorder of ketone body formation. Here, we report high-resolution crystal structures of the human cytosolic (hHMGCS1) and mitochondrial (hHMGCS2) isoforms in binary product complexes. Our data represent the first structures solved for human HMGCS and the mitochondrial isoform, allowing for the first time structural comparison among the three isoforms. This serves as a starting point for the development of isoform-specific inhibitors that have potential cholesterol-reducing and antibiotic applications. In addition, missense mutations that cause mitochondrial HMGCS deficiency have been mapped onto the hHMGCS2 structure to rationalize the structural basis for the disease pathology.
-===CRYSTAL STRUCTURE OF HUMAN MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A SYNTHASE 2 (HMGCS2)===
+Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design.,Shafqat N, Turnbull A, Zschocke J, Oppermann U, Yue WW J Mol Biol. 2010 May 14;398(4):497-506. Epub 2010 Mar 25. PMID:20346956<ref>PMID:20346956</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_20346956}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 2wya" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 20346956 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20346956}}
+__TOC__
+</StructureSection>
-==About this Structure==
-WYA is a 4 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2v4w 2v4w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WYA OCA].
-==Reference==
-<ref group="xtra">PMID:20346956</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Hydroxymethylglutaryl-CoA synthase]]
+[[Category: Large Structures]]
-[[Category: Arrowsmith, C.]]
+[[Category: Arrowsmith C]]
-[[Category: Bountra, C.]]
+[[Category: Bountra C]]
-[[Category: Cooper, C.]]
+[[Category: Cooper C]]
-[[Category: Delft, F Von.]]
+[[Category: Edwards A]]
-[[Category: Edwards, A.]]
+[[Category: Murray JW]]
-[[Category: Murray, J W.]]
+[[Category: Oppermann U]]
-[[Category: Oppermann, U.]]
+[[Category: Roos AK]]
-[[Category: Roos, A K.]]
+[[Category: Savitsky P]]
-[[Category: Savitsky, P.]]
+[[Category: Shafqat N]]
-[[Category: Shafqat, N.]]
+[[Category: Wikstrom M]]
-[[Category: Wikstrom, M.]]
+[[Category: Yue WW]]
-[[Category: Yue, W W.]]
+[[Category: Von Delft F]]
-[[Category: Acetylation]]
-[[Category: Cholesterol biosynthesis]]
-[[Category: Disease mutation]]
-[[Category: Lipid synthesis]]
-[[Category: Melavonate pathway]]
-[[Category: Mitochondria]]
-[[Category: Mitochondrion]]
-[[Category: Phosphoprotein]]
-[[Category: Steroid biosynthesis]]
-[[Category: Sterol biosynthesis]]
-[[Category: Thiolase]]
-[[Category: Transferase]]
-[[Category: Transit peptide]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 14 09:04:45 2010''