PMID: 10451545Aug 19, 1999Paper

Molecular dynamics simulations of human glutathione transferase P1-1: analysis of the induced-fit mechanism by GSH binding

Proteins
Lorenzo StellaE E Di Iorio

Abstract

We report here a 1-ns molecular dynamics simulation on the ligand-free monomer of human glutathione transferase P1-1 in bulk water. The average conformation obtained from the last 500 ps of simulation is taken as a model for the apo-structure of this protein and compared to the available crystallographic data. Remarkable changes in the tertiary structure take place during the simulation and are ascribed to the removal of the ligand. They support an induced fit mechanism occurring upon glutathione binding, whose major features can be described in detail. A portion of helix 2 (residues 42-50), which participates in the formation of the active site, undergoes the most prominent conformational changes. Other protein segments, such as the C-terminal loop and helix 4, also show relevant structural rearrangements. All these transitions cause a significant shielding from the solvent of the hydrophobic binding site of the co-substrate, whose exposed surface goes from 4.6 nm(2) in the holo-structure to about 3.1 nm(2) in the apo-conformation. The results of this simulation are consistent with numerous experimental observations previously obtained on GST P1-1 and provide new insights for their explanation at the molecular level. Proteins ...Continue Reading

References

May 22, 1992·Biochimica Et Biophysica Acta·M Lo BelloG Federici
Dec 1, 1990·Biopolymers·R E Bruccoleri, M Karplus
Mar 16, 1994·Biochimica Et Biophysica Acta·M C Wilce, M W Parker
Feb 1, 1996·Journal of Molecular Graphics·R KoradiK Wüthrich
Oct 15, 1996·Structure·W A EatonJ Hofrichter

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