6cer: Difference between revisions

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 <StructureSection load='6cer' size='340' side='right' caption='[[6cer]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6cer]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CER OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CER FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6cer]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CER OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CER FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TDP:THIAMIN+DIPHOSPHATE'>TDP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ni4|1ni4]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDHA1, PHE1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PDHB, PHE1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyruvate_dehydrogenase_(acetyl-transferring) Pyruvate dehydrogenase (acetyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.1 1.2.4.1] </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=6cer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cer OCA], [http://pdbe.org/6cer PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cer RCSB], [http://www.ebi.ac.uk/pdbsum/6cer PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cer ProSAT]</span></td></tr>
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 == Function ==
 [[http://www.uniprot.org/uniprot/ODPA_HUMAN ODPA_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.<ref>PMID:7782287</ref> <ref>PMID:19081061</ref>  [[http://www.uniprot.org/uniprot/ODPB_HUMAN ODPB_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.<ref>PMID:17474719</ref> <ref>PMID:19081061</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The pyruvate dehydrogenase multienzyme complex (PDHc) connects glycolysis to the tricarboxylic acid cycle by producing acetyl-CoA via the decarboxylation of pyruvate. Because of its pivotal role in glucose metabolism, this complex is closely regulated in mammals by reversible phosphorylation, the modulation of which is of interest in treating cancer, diabetes, and obesity. Mutations such as that leading to the alphaV138M variant in pyruvate dehydrogenase, the pyruvate-decarboxylating PDHc E1 component, can result in PDHc deficiency, an inborn error of metabolism that results in an array of symptoms such as lactic acidosis, progressive cognitive and neuromuscular deficits, and even death in infancy or childhood. Here we present an analysis of two X-ray crystal structures at 2.7 A resolution, the first of the disease-associated human alphaV138M E1 variant and the second of human wild-type (WT) E1 with a bound adduct of its coenzyme thiamin diphosphate (ThDP) and the substrate analogue acetylphosphinate (AcPhi). The structures provide support for the role of regulatory loop disorder in E1 inactivation, and the alphaV138M variant structure also reveals that altered coenzyme binding can result in such disorder even in the absence of phosphorylation. Specifically, both E1 phosphorylation at alphaSer264 and the alphaV138M substitution result in disordered loops that are not optimally oriented or available to efficiently bind the lipoyl domain of PDHc E2. Combined with an analysis of alphaV138M activity, these results underscore the general connection between regulatory loop disorder and loss of E1 catalytic efficiency.
+Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the alphaV138M variant of human pyruvate dehydrogenase.,Whitley MJ, Arjunan P, Nemeria NS, Korotchkina LG, Park YH, Patel M, Jordan F, Furey WF J Biol Chem. 2018 Jul 3. pii: RA118.003996. doi: 10.1074/jbc.RA118.003996. PMID:29970614<ref>PMID:29970614</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6cer" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Arjunan, P]]
 [[Category: Furey, W]]