View source for 7rde


==Human Triose Phosphate Isomerase Q181P==
<StructureSection load='7rde' size='340' side='right'caption='[[7rde]], [[Resolution|resolution]] 1.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rde]] 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=7RDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RDE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.31&#8491;</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=CA:CALCIUM+ION'>CA</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=7rde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rde OCA], [https://pdbe.org/7rde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rde RCSB], [https://www.ebi.ac.uk/pdbsum/7rde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rde ProSAT]</span></td></tr>
</table>
== Disease ==
[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;">
== Publication Abstract from PubMed ==
Triosephosphate isomerase (TPI) deficiency (TPI Df) is an untreatable glycolytic enzymopathy that results in hemolytic anemia, progressive muscular impairment and irreversible brain damage. Although there is a 'common' mutation (TPIE105D), other pathogenic mutations have been described. We identified patients who were compound heterozygous for a newly described mutation, TPIQ181P, and the common TPIE105D mutation. Intriguingly, these patients lacked neuropathy or cognitive impairment. We then initiated biochemical and structural studies of TPIQ181P. Surprisingly, we found that purified TPIQ181P protein had markedly impaired catalytic properties whereas crystallographic studies demonstrated that the TPIQ181P mutation resulted in a highly disordered catalytic lid. We propose that genetic complementation occurs between the two alleles, one with little activity (TPIQ181P) and one with low stability (TPIE105D). Consistent with this, TPIQ181P/E105D fibroblasts exhibit a significant reduction in the TPI protein. These data suggest that impaired stability, and not catalytic activity, is a better predictor of TPI Df severity. Lastly, we tested two recently discovered chemical modulators of mutant TPI stability, itavastatin and resveratrol, and observed a significant increase in TPI in TPIQ181P/E105D patient cells.

Itavastatin and resveratrol increase triosephosphate isomerase protein in a newly identified variant of TPI deficiency.,VanDemark AP, Hrizo SL, Eicher SL, Kowalski J, Myers TD, Pfeifer MR, Riley KN, Koeberl DD, Palladino MJ Dis Model Mech. 2022 May 1;15(5). pii: 274792. doi: 10.1242/dmm.049261. Epub 2022, May 17. PMID:35315486<ref>PMID:35315486</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7rde" style="background-color:#fffaf0;"></div>

==See Also==
*[[Triose phosphate isomerase 3D structures|Triose phosphate isomerase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kowalski J]]
[[Category: VanDemark AP]]