Structural highlights
Publication Abstract from PubMed
Despite extensive research on triosephosphate isomerase (TIM), there exists a gap in understanding the remarkable conjunction between catalytic loop-6 (residue 166-176) movement and conformational flip of Glu165 (catalytic base) upon substrate binding, thus priming the active site for efficient catalysis. The overwhelming occurrence of Ser at position 96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residue, Phe, at this position and curiously, the mutant F96S was catalytically defective. We provide insights into the influence of residue 96 on the loop-6 dynamics and E165 positioning by combining the kinetic and structural studies on the PfTIM F96 mutants, F96Y, F96A, F96S/S73A and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.
Connecting active site loop conformations and catalysis in triosephosphate isomerase: insights from a rare variation at residue 96 in the plasmodial enzyme.,Pareek V, Samanta M, Joshi NV, Balaram H, Murthy MR, Balaram P Chembiochem. 2016 Jan 14. doi: 10.1002/cbic.201500532. PMID:26762569[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pareek V, Samanta M, Joshi NV, Balaram H, Murthy MR, Balaram P. Connecting active site loop conformations and catalysis in triosephosphate isomerase: insights from a rare variation at residue 96 in the plasmodial enzyme. Chembiochem. 2016 Jan 14. doi: 10.1002/cbic.201500532. PMID:26762569 doi:http://dx.doi.org/10.1002/cbic.201500532
