Function of Conserved Residues of Human Glutathione Synthetase: Implications for the ATP-grasp Enzymes

Description:

This article discusses human glutathione synthetase, an enzyme that belongs to the glutathione synthetase ATP-binding domain-like superfamily.

Creator(s):
Creation Date: February 27, 2004
Partner(s):
UNT College of Arts and Sciences
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UNT Scholarly Works
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Creator (Author):
Dinescu, Adriana

University of North Texas

Creator (Author):
Cundari, Thomas R., 1964-

University of North Texas

Creator (Author):
Bhansali, Vikas S.

University of North Texas

Creator (Author):
Luo, Jia-Li

Hisun Pharmaceutical Co. Ltd.

Creator (Author):
Anderson, Mary E.

Texas Woman's University

Publisher Info:
Place of Publication: [Rockville, Maryland]
Date(s):
  • Creation: February 27, 2004
Description:

This article discusses human glutathione synthetase, an enzyme that belongs to the glutathione synthetase ATP-binding domain-like superfamily.

Degree:
Department: Chemistry
Note:

Abstract: Glutathione synthetase is an enzyme that belongs to the glutathione synthetase ATP-binding domain-like superfamily. It catalyzes the second step in the biosynthesis of glutathione from y-glutamylcysteine and glycine in an ATP-dependent manner. Glutathione synthetase has been purified and sequenced from a variety of biological sources; still, its exact mechanism is not fully understood. A variety of structural alignment methods were applied and four highly conserved residues of human glutathione synthetase (Glu-144, Asn-146, Lys-305, and Lys-364) were identified in the binding site. The function of these was studied by experimental and computational site-directed mutagenesis. The three-dimensional coordinates for several human glutathione synthetase mutant enzymes were obtained using molecular mechanics and molecular dynamics simulation techniques, starting from the reported crystal structure of human glutathione synthetase. Consistent with circular dichroism spectroscopy, the authors' results showed no major changes to overall enzyme structure upon residue mutation. However, semiempirical calculations revealed that ligand binding is affected by these mutations. The key interactions between conserved residues and ligands were detected and found to be essential for enzymatic activity. Particularly, the negatively charged Glu-144 residue plays a major role in catalysis.

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Keyword(s): glutathione synthetase | enzymes
Source: Journal of Biological Chemistry, 2004, Rockville: American Society for Biochemistry and Molecular Biology, pp. 22412-22421
Partner:
UNT College of Arts and Sciences
Collection:
UNT Scholarly Works
Identifier:
  • DOI: 10.1074/jbc.M401334200 |
  • ARK: ark:/67531/metadc75414
Resource Type: Article
Format: Text
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Access: Public
Citation:
Publication Title: Journal of Biological Chemistry
Volume: 279
Issue: 21
Page Start: 22412
Page End: 22421
Pages: 10
Peer Reviewed: Yes