2vgi

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[[Image:2vgi.jpg|left|200px]]
 
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==HUMAN ERYTHROCYTE PYRUVATE KINASE: R486W MUTANT==
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The line below this paragraph, containing "STRUCTURE_2vgi", creates the "Structure Box" on the page.
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<StructureSection load='2vgi' size='340' side='right'caption='[[2vgi]], [[Resolution|resolution]] 2.87&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2vgi]] 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=1lix 1lix]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VGI FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.87&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PGA:2-PHOSPHOGLYCOLIC+ACID'>PGA</scene></td></tr>
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{{STRUCTURE_2vgi| PDB=2vgi | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vgi OCA], [https://pdbe.org/2vgi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vgi RCSB], [https://www.ebi.ac.uk/pdbsum/2vgi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vgi ProSAT]</span></td></tr>
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</table>
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'''HUMAN ERYTHROCYTE PYRUVATE KINASE: R486W MUTANT'''
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== Disease ==
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[https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Defects in PKLR are the cause of pyruvate kinase hyperactivity (PKHYP) [MIM:[https://omim.org/entry/102900 102900]; also known as high red cell ATP syndrome. This autosomal dominant phenotype is characterized by increase of red blood cell ATP.<ref>PMID:9090535</ref> Defects in PKLR are the cause of pyruvate kinase deficiency of red cells (PKRD) [MIM:[https://omim.org/entry/266200 266200]. A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.
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== Function ==
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==Overview==
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[https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Plays a key role in glycolysis (By similarity).
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Deficiency of human erythrocyte isozyme (RPK) is, together with glucose-6-phosphate dehydrogenase deficiency, the most common cause of the nonspherocytic hemolytic anemia. To provide a molecular framework to the disease, we have solved the 2.7 A resolution crystal structure of human RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and phosphoglycolate, a substrate analogue, and we have functionally and structurally characterized eight mutants (G332S, G364D, T384M, D390N, R479H, R486W, R504L, and R532W) found in RPK-deficient patients. The mutations target distinct regions of RPK structure, including domain interfaces and catalytic and allosteric sites. The mutations affect to a different extent thermostability, catalytic efficiency, and regulatory properties. These studies are the first to correlate the clinical symptoms with the molecular properties of the mutant enzymes. Mutations greatly impairing thermostability and/or activity are associated with severe anemia. Some mutant proteins exhibit moderate changes in the kinetic parameters, which are sufficient to cause mild to severe anemia, underlining the crucial role of RPK for erythrocyte metabolism. Prediction of the effects of mutations is difficult because there is no relation between the nature and location of the replaced amino acid and the type of molecular perturbation. Characterization of mutant proteins may serve as a valuable tool to assist with diagnosis and genetic counseling.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==About this Structure==
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Check<jmol>
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2VGI is a [[Single protein]] structure of sequence 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=1lix 1lix]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VGI OCA].
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vg/2vgi_consurf.spt"</scriptWhenChecked>
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==Reference==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia., Valentini G, Chiarelli LR, Fortin R, Dolzan M, Galizzi A, Abraham DJ, Wang C, Bianchi P, Zanella A, Mattevi A, J Biol Chem. 2002 Jun 28;277(26):23807-14. Epub 2002 Apr 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11960989 11960989]
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2vgi ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Pyruvate kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Abraham DJ]]
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[[Category: Abraham, D J.]]
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[[Category: Bianchi P]]
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[[Category: Bianchi, P.]]
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[[Category: Chiarelli L]]
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[[Category: Chiarelli, L.]]
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[[Category: Dolzan M]]
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[[Category: Dolzan, M.]]
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[[Category: Fortin R]]
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[[Category: Fortin, R.]]
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[[Category: Galizzi A]]
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[[Category: Galizzi, A.]]
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[[Category: Mattevi A]]
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[[Category: Mattevi, A.]]
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[[Category: Valentini G]]
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[[Category: Valentini, G.]]
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[[Category: Wang C]]
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[[Category: Wang, C.]]
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[[Category: Zanella A]]
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[[Category: Zanella, A.]]
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[[Category: Alternative splicing]]
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[[Category: Disease mutation]]
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[[Category: Glycolysis]]
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[[Category: Kinase]]
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[[Category: Magnesium]]
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[[Category: Metal-binding]]
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[[Category: Phosphorylation]]
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[[Category: Polymorphism]]
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[[Category: Pyruvate]]
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[[Category: Pyruvate kinase in the active r-state]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 18:46:02 2008''
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Current revision

HUMAN ERYTHROCYTE PYRUVATE KINASE: R486W MUTANT

PDB ID 2vgi

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