7rde | pdb_00007rde

Human Triose Phosphate Isomerase Q181P

spinqualitylabelsall models 7rde, resolution 1.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rde is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BR, CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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) 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Triose phosphate isomerase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA