Biophysical Journal 64: 9-15 (1993)
© 1993 the Biophysical Society

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Related articles in Biophys. J. Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wade, R C Articles by McCammon, J A Search for Related Content PubMed PubMed Citation Articles by Wade, R C Articles by McCammon, J A

Gating of the active site of triose phosphate isomerase: Brownian dynamics simulations of flexible peptide loops in the enzyme.

Department of Chemistry, University of Houston, Texas 77204-5641.

ABSTRACT

The enzyme triose phosphate isomerase has flexible peptide loops at its active sites. The loops close over these sites upon substrate binding, suggesting that the dynamics of the loops could be of mechanistic and kinetic importance. To investigate these issues, the loop motions in the dimeric enzyme were simulated by Brownian dynamics. The two loops, one on each monomer, were represented by linear chains of appropriately parameterized spheres, each sphere corresponding to an amino acid residue. The loops moved in the electrostatic field of the rest of the enzyme, which was held rigid in its crystallographically observed conformation. In the absence of substrate, the loops exhibited gating of the active site with a period of about 1 ns and occupied "closed" conformations for about half of the time. As the period of gating is much shorter than the enzyme-substrate relaxation time, the motion of the loops does not reduce the rate constant for the approach of substrate from its simple diffusion-controlled value. This suggests that the flexible loops may have evolved to create the appropriate environment for catalysis while, at the same time, minimizing the kinetic penalty for gating the active site.

Related articles in Biophys. J.:

A commentary on gating of the active site of triose phosphate isomerase: Brownian dynamics simulations of flexible peptide loops in the enzyme, by R. C. Wade, M. E. Davis, B. A. Luty, J. D. Madura, and J. A. McCammon.

S A Allison
Biophys. J. 1993 64: 1-2. [PDF]  

This article has been cited by other articles:

				J. Trylska, V. Tozzini, C.-e. A. Chang, and J. A. McCammon HIV-1 Protease Substrate Binding and Product Release Pathways Explored with Coarse-Grained Molecular Dynamics Biophys. J., June 15, 2007; 92(12): 4179 - 4187. [Abstract] [Full Text] [PDF]

				Y. Cheng, J. K. Suen, D. Zhang, S. D. Bond, Y. Zhang, Y. Song, N. A. Baker, C. L. Bajaj, M. J. Holst, and J. A. McCammon Finite Element Analysis of the Time-Dependent Smoluchowski Equation for Acetylcholinesterase Reaction Rate Calculations Biophys. J., May 15, 2007; 92(10): 3397 - 3406. [Abstract] [Full Text] [PDF]

				C.-E. Chang, T. Shen, J. Trylska, V. Tozzini, and J. A. McCammon Gated Binding of Ligands to HIV-1 Protease: Brownian Dynamics Simulations in a Coarse-Grained Model Biophys. J., June 1, 2006; 90(11): 3880 - 3885. [Abstract] [Full Text] [PDF]

				S. Sacquin-Mora and R. Lavery Investigating the Local Flexibility of Functional Residues in Hemoproteins Biophys. J., April 15, 2006; 90(8): 2706 - 2717. [Abstract] [Full Text] [PDF]

				Y. Song, Y. Zhang, T. Shen, C. L. Bajaj, J. A. McCammon, and N. A. Baker Finite Element Solution of the Steady-State Smoluchowski Equation for Rate Constant Calculations Biophys. J., April 1, 2004; 86(4): 2017 - 2029. [Abstract] [Full Text] [PDF]

				S. Parthasarathy, K. Eaazhisai, H. Balaram, P. Balaram, and M. R. N. Murthy Structure of Plasmodium falciparum Triose-phosphate Isomerase-2-Phosphoglycerate Complex at 1.1-A Resolution J. Biol. Chem., December 26, 2003; 278(52): 52461 - 52470. [Abstract] [Full Text] [PDF]