Triose Phosphate Isomerase: Difference between revisions

'''Role in Alzheimer's Disease''': Recent discoveries in Alzheimer Disease research has indicated that amyloid beta-peptide induced nitro-oxidative damage promotes the nitrotyrosination of the glycolytic enzyme triosephosphate isomerase in human neuroblastoma cells.<ref>PMID:19251756</ref> nitro-triosephosphate isomerase was found to be present in brain slides from double transgenic mice overexpressing human amyloid precursor protein as well as in Alzheimer's disease patients. Specifically, the nitrotyrosination occurs on <scene name='Triose_Phosphate_Isomerase/Two_tyrosines_shaded/2'>Tyr164 and Tyr208</scene> , which are located in close proximity to the catalytic center, and this modification correlates with a reduced isomerase activity. Additionally, according to work done by Francesc Guix and colleagues, nitro-triosphosphate isomerase contributed to the formation of large beta-sheet aggregates ''in vitro'' and ''in vivo''.

Due to its role in the glycolysis, an essential process to many organisms, TPI has been isolated and crystallized from several species giving rise to extensive multiple alignment ''in silico'' experiments which subsequently provided <scene name='Triose_Phosphate_Isomerase/Conserved/1'>amino acid conservation structures</scene> of TPI. <ref>PMID:12403619</ref> Collectively, these tools have determined that TPI has a roughly 50% sequence conservation from bacteria to humans.<ref>PMID:8130194</ref> One specific example of sequence homology is that of loop 6 and loop 7 residues, whose structural contributions are discussed above. In a sequence alignment of 133 TIM sequences, two highly conserved motifs are noticed.  First, 114 sequences in loop 6 contain the PXW sequence family (where X is I,L or V in 112 sequences or otherwise a T or K). Secondly, loop 7 contains a highly conserved YGGS motif; however, this motif is only found when the N-terminal hinge contains tryptophan.