3exi: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:3exi.png|left|200px]]
-<!--
+==Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complex with the subunit-binding domain (SBD) of E2p, but SBD cannot be modeled into the electron density==
-The line below this paragraph, containing "STRUCTURE_3exi", creates the "Structure Box" on the page.
+<StructureSection load='3exi' size='340' side='right'caption='[[3exi]], [[Resolution|resolution]] 2.20&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'>[[3exi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EXI 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]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
-{{STRUCTURE_3exi|  PDB=3exi  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3exi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3exi OCA], [https://pdbe.org/3exi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3exi RCSB], [https://www.ebi.ac.uk/pdbsum/3exi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3exi ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ODPA_HUMAN ODPA_HUMAN] Defects in PDHA1 are a cause of pyruvate dehydrogenase E1-alpha deficiency (PDHAD) [MIM:[https://omim.org/entry/312170 312170]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.<ref>PMID:1338114</ref> <ref>PMID:1909401</ref> <ref>PMID:1551669</ref> <ref>PMID:1293379</ref> <ref>PMID:8504306</ref> <ref>PMID:8032855</ref> <ref>PMID:7545958</ref> <ref>PMID:7967473</ref> <ref>PMID:7887409</ref> <ref>PMID:7573035</ref> <ref>PMID:7757088</ref> <ref>PMID:8664900</ref> <ref>PMID:8844217</ref> <ref>PMID:9671272</ref>   Defects in PDHA1 are the cause of X-linked Leigh syndrome (X-LS) [MIM:[https://omim.org/entry/308930 308930]. X-LS is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation. LS may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes.<ref>PMID:1909401</ref> <ref>PMID:7887409</ref> <ref>PMID:8498846</ref> <ref>PMID:8199595</ref> <ref>PMID:9266390</ref>
+== Function ==
+[https://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>
+== 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/ex/3exi_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=3exi ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+We report the crystal structures of the phosporylated pyruvate dehydrogenase (E1p) component of the human pyruvate dehydrogenase complex (PDC). The complete phosphorylation at Ser264-alpha (site 1) of a variant E1p protein was achieved using robust pyruvate dehydrogenase kinase 4 free of the PDC core. We show that unlike its unmodified counterpart, the presence of a phosphoryl group at Ser264-alpha prevents the cofactor thiamine diphosphate-induced ordering of the two loops carrying the three phosphorylation sites. The disordering of these phosphorylation loops is caused by a previously unrecognized steric clash between the phosphoryl group at site 1 and a nearby Ser266-alpha, which nullifies a hydrogen-bonding network essential for maintaining the loop conformations. The disordered phosphorylation loops impede the binding of lipoyl domains of the PDC core to E1p, negating the reductive acetylation step. This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine.
-===Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complex with the subunit-binding domain (SBD) of E2p, but SBD cannot be modeled into the electron density===
+Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops.,Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061<ref>PMID:19081061</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3exi" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-EXI is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EXI OCA].
+*[[Pyruvate dehydrogenase 3D structures|Pyruvate dehydrogenase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Chuang, D T.]]
+[[Category: Large Structures]]
-[[Category: Chuang, J L.]]
+[[Category: Chuang DT]]
-[[Category: Kato, M.]]
+[[Category: Chuang JL]]
-[[Category: Li, J.]]
+[[Category: Kato M]]
-[[Category: Machius, M.]]
+[[Category: Li J]]
-[[Category: Tso, S C.]]
+[[Category: Machius M]]
-[[Category: Wynn, R M.]]
+[[Category: Tso S-C]]
-[[Category: Alternative splicing]]
+[[Category: Wynn RM]]
-[[Category: Disease mutation]]
-[[Category: Glycolysis]]
-[[Category: Heterotetramer]]
-[[Category: Leigh syndrome]]
-[[Category: Mitochondrion]]
-[[Category: Oxidoreductase]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Pyruvate]]
-[[Category: Thiamine diphosphate-dependent enzyme]]
-[[Category: Thiamine pyrophosphate]]
-[[Category: Transit peptide]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 18 20:27:31 2009''