Computational study of the ground state of thermophilic indole glycerol phosphate synthase: structural alterations at the active site with temperature.
Hyperthermophlic indole-3-glycerol phosphate synthase (IGPS) catalyzes the terminal ring-closure step in tryptophan biosynthesis. In this paper, we compare the results from the molecular dynamics (MD) simulation of enzyme-bound substrate at 298 K (E.S298) and 385 K (E.S385) solvated in the TIP3P water box using the CHARMM force field to address the question of the structural change of the Enzyme. Substrate complex with temperature. The population of the reactive Enzyme. Substrate conformers (near attack conformers or NACs) increases by approximately 1100-fold in going from room temperature (E.S298) to high temperature (E.S385). This increased population of NAC conformers in the Michaelis complex correlates well with the increase in rate in going from 298 to 385 K. The positioning of the two active site residues Lys53 and Lys110 controls binding of the substrate in the favorable orientation for general acid-catalyzed intramolecular ring formation reaction. It can be concluded that the NAC formation allowing general acid catalysis has much to do with the temperature dependence of the free energy of reaction.
Mazumder-Shivakumar
Devleena
D
Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, USA.
Kahn
Kalju
K
Bruice
Thomas C
TC
D001105:Archaea / Q000201:enzymology; D001665:Binding Sites; D019295:Computational Biology; D007209:Indole-3-Glycerol-Phosphate Synthase / Q000737:chemistry*; D007700:Kinetics; D011487:Protein Conformation; D013696:Temperature
D007209:Indole-3-Glycerol-Phosphate Synthase