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| | ==Structure of human triose phosphate isomerase K13M== | | ==Structure of human triose phosphate isomerase K13M== |
| - | <StructureSection load='4zvj' size='340' side='right' caption='[[4zvj]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4zvj' size='340' side='right'caption='[[4zvj]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zvj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZVJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zvj]] 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=4ZVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZVJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.6996Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=4zvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvj OCA], [http://pdbe.org/4zvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zvj RCSB], [http://www.ebi.ac.uk/pdbsum/4zvj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvj 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=4zvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvj OCA], [https://pdbe.org/4zvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zvj RCSB], [https://www.ebi.ac.uk/pdbsum/4zvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN]] Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:[http://omim.org/entry/190450 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. | + | [https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN] Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:[https://omim.org/entry/190450 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. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4zvj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4zvj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Triose phosphate isomerase 3D structures|Triose phosphate isomerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Triose-phosphate isomerase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Amrich, C G]] | + | [[Category: Large Structures]] |
| - | [[Category: Heroux, A]] | + | [[Category: Amrich CG]] |
| - | [[Category: Smith, C]] | + | [[Category: Heroux A]] |
| - | [[Category: VanDemark, A P]]
| + | [[Category: Smith C]] |
| - | [[Category: Dimer]] | + | [[Category: VanDemark AP]] |
| - | [[Category: Glycolysis]] | + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Tim]]
| + | |
| - | [[Category: Triose phosphate isomerase]]
| + | |
| Structural highlights
Disease
TPIS_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.
Function
TPIS_HUMAN
Publication Abstract from PubMed
Triosephosphate 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 Also
References
- ↑ Roland BP, Amrich CG, Kammerer CJ, Stuchul KA, Larsen SB, Rode S, Aslam AA, Heroux A, Wetzel R, VanDemark AP, Palladino MJ. Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency. Biochim Biophys Acta. 2015 Jan;1852(1):61-9. doi: 10.1016/j.bbadis.2014.10.010., Epub 2014 Oct 16. PMID:25463631 doi:http://dx.doi.org/10.1016/j.bbadis.2014.10.010
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