4pod: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4pod]] 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=4POD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4POD FirstGlance]. <br> | <table><tr><td colspan='2'>[[4pod]] 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=4POD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4POD FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4pod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pod OCA], [https://pdbe.org/4pod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pod RCSB], [https://www.ebi.ac.uk/pdbsum/4pod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pod ProSAT]</span></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=4pod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pod OCA], [https://pdbe.org/4pod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pod RCSB], [https://www.ebi.ac.uk/pdbsum/4pod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pod ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 20:19, 20 September 2023
Structure of Triosephosphate Isomerase I170V mutant human enzyme.Structure of Triosephosphate Isomerase I170V mutant human enzyme.
Structural highlights
DiseaseTPIS_HUMAN Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:190450. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection. FunctionPublication Abstract from PubMedTriosephosphate isomerase (TPI) is a glycolytic enzyme which homodimerizes for full catalytic activity. Mutations of the TPI gene elicit a disease known as TPI Deficiency, a glycolytic enzymopathy noted for its unique severity of neurological symptoms. Evidence suggests that TPI Deficiency pathogenesis may be due to conformational changes of the protein, likely affecting dimerization and protein stability. In this report, we genetically and physically characterize a human disease-associated TPI mutation caused by an I170V substitution. Human TPI(I170V) elicits behavioral abnormalities in Drosophila. An examination of hTPI(I170V) enzyme kinetics revealed this substitution reduced catalytic turnover, while assessments of thermal stability demonstrated an increase in enzyme stability. The crystal structure of the homodimeric I170V mutant reveals changes in the geometry of critical residues within the catalytic pocket. Collectively these data reveal new observations of the structural and kinetic determinants of TPI Deficiency pathology, providing new insights into disease pathogenesis. Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency.,Roland BP, Amrich CG, Kammerer CJ, Stuchul KA, Larsen SB, Rode S, Aslam AA, Heroux A, Wetzel R, VanDemark AP, Palladino MJ Biochim Biophys Acta. 2015 Jan;1852(1):61-9. doi: 10.1016/j.bbadis.2014.10.010., Epub 2014 Oct 16. PMID:25463631[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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