Glutathione synthetase: Conserved residues of the substrate loop

The important antioxidant tripeptide glutathione (GSH) is synthesized in two ATP-dependent steps; the second enzyme in the biosynthetic pathway, glutathione synthetase (GS), ligates glycine to γ-glutamylcysteine (γ-GC). Human glutathione synthetase (hGS) deficiency causes hemolytic anemia, metabolic acidosis, 5-oxprolinuria and a total deficiency may be lethal. Three flexible loops (A, G and S) surround the substrates (ATP, glycine and γ-GC). Human glutathione synthetase is negatively cooperative to one substrate, γ-GC. The Substrate- or S-loop is proximal to γ-GC and thought to participate in γ-GC binding. The S-loop (266-FRDGYMPRQYS-276) contains 11 residues, some of which are highly conserved (F266, R267, G269, Y270, P272 and Y275). Site directed mutagenesis was used to change these highly conserved S-loop residues, and then their roles in substrate binding, enzyme activity and stability were assessed.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Master

Discipline thesis:degree_discipline

Chemistry

Grantor

Texas Woman's University

Year dc:date.issued

2013

Author dc:creator

• Shrestha, Bisesh

Chair dc:contributor.committeechair

• Anderson, Mary

Committee members dc:contributor.committeemember

• Britt, Mark
• Anderson, Mary E.
• Sheardy, Richard Dean

• Pure sciences
• Biological sciences
• Active site
• Anion-pi
• Arginine
• Cooperativity
• Glutathione synthetase
• Tryptophan

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/11274/11084

OAI identifier oai:identifier

oai:twu-ir.tdl.org:11274/11084