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Loop Interaction in Human Glutathione Synthetase
Author(s) -
Dinescu Adriana,
Cundari Thomas R.,
Anderson Mary E.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a473-a
Subject(s) - cysteine , glutathione , glycine , loop (graph theory) , chemistry , ligand (biochemistry) , glutathione synthetase , alanine , molecular dynamics , active site , stereochemistry , biophysics , enzyme , amino acid , computational chemistry , biochemistry , biology , receptor , mathematics , combinatorics
The free and reactant forms of human glutathione synthetase (hGS) were modeled computationally by the use of molecular dynamics (MD) techniques, as these currently have not been structurally characterized. Together with the reported product structure of the enzyme, the free and reactant structures of hGS generate a complete reaction cycle for glutathione formation from gamma‐glutamyl‐cysteine and glycine. Our analysis of loop motion during the reaction cycle provides an insight into the role of loop residues in ligand binding. Interestingly, the results of MD simulations showed that the central fragments of the glycine‐rich and alanine‐rich loops have a double role in the reactant conformation : they bind the substrates and simultaneously interact with each other through an extensive network of hydrogen bonds. The present study proposes that these favorable loop‐ligand and loop‐loop interactions are required for opening and closing of the active site of hGS. This research was supported by funds from the University of North Texas, U.S. Department of Education, a Faculty Research Enhancement Grant (MEA) from Texas Woman’s University, and a Welch Foundation Departmental grant to Chemistry at TWU.