Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase.

Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Abstract Text:

Yi Yang,Ying Chen,Elisabet Johansson,Scott N Schneider,Howard G Shertzer,Daniel W Nebert,Timothy P Dalton,

Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the glutathione (GSH) biosynthesis pathway. This enzyme is a heterodimer, comprising a catalytic subunit (GCLC) and a regulatory subunit (GCLM). Although GCLC alone can catalyze the formation of l-gamma-glutamyl-l-cysteine, its binding with GCLM enhances the enzyme activity by lowering the K(m) for glutamate and ATP, and increasing the K(i) for GSH inhibition. To characterize the enzyme structure-function relationship, we investigated the heterodimer formation between GCLC and GCLM, in vivo using the yeast two-hybrid system, and in vitro using affinity chromatography. A strong and specific interaction between GCLC and GCLM was observed in both systems. Deletion analysis indicated that most regions, except a portion of the C-terminal region of GCLC and a portion of the N-terminal region of GCLM, are required for the interaction to occur. Point mutations of selected amino acids were also tested for the binding activity. The GCLC Cys248Ala/Cys249Ala and Pro158Leu mutations enzyme showed the same strength of binding to GCLM as did wild-type GCLC, yet the catalytic activity was dramatically decreased. The results suggest that the heterodimer formation may not be dependent on primary amino-acid sequence but, instead, involves a complex formation of the tertiary structure of both proteins.

Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Publishing Authors By Initials

Y Yang,Y Chen,E Johansson,SN Schneider,HG Shertzer,DW Nebert,TP Dalton,

For similar investigative techniques: genetic techniques: cloning, molecular: two-hybrid system techniques research abstracts see: investigative techniques: genetic techniques: cloning, molecular: two-hybrid system techniques research

PUBMED ID PMID:

MEDLINE DATE:

Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemical pharmacology

VOLUME: 74

Page Numbers: 372-81

Journal Abbreviation: Biochem. Pharmacol.

ISSN: 0006-2952

DAY: 12

MONTH: 02

YEAR: 2007

Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101032

Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Keywords Mesh Terms:

KEYWORDS: Two-Hybrid System Techniques

MESH TERMS: genetics

Chemical & Substance for Abstract: Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Information

Substance Name: Glutamate-Cysteine Ligase

Registry Number: EC 6.3.2.2

Grant and Affiliation Information for Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase.

AFFILIATION: Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati OH 45267-005, United States.

Country: England

AGENCY: United States NIEHS

GRANT: R01 ES10416

ACRONYM: ES

MEDLINETA: Biochem Pharmacol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase Related Publications

• 7H-dibenzo[c,g]carbazole metabolism by the mouse and human CYP1 family of enzymes.
• A ligand-based approach to identify quantitative structure-activity relationships for the androgen receptor.
• Archaeology: pieces of the puzzle.
• Boosting morale and improving performance in the nursing setting.
• Children with a TV in their bedroom at higher risk for being overweight.
• Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia.
• Crystal structure of the T877A human androgen receptor ligand-binding domain complexed to cyproterone acetate provides insight for ligand-induced conformational changes and structure-based drug design.
• Demand and supply of bone allograft and the role of orthopaedic surgeons.
• Drug insight: Testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging.
• Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs).
• Flavor Processing: Perceptual and Cognitive Factors in Multi-modal Integration.
• Geology: mine games.
• Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure.
• IFN-gamma acts directly on activated CD4+ T cells during mycobacterial infection to promote apoptosis by inducing components of the intracellular apoptosis machinery and by inducing extracellular proapoptotic signals.
• Improving measurement of normative beliefs involving smoking among adolescents.
• In vivo metabolism and final disposition of a novel nonsteroidal androgen in rats and dogs.
• Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase.
• Laws under review for fossils on native land.
• Low-V(pi) electro-optic modulator with a high-microbeta chromophore and a constant-bias field.
• Numerical modeling of nasal obstruction and endoscopic surgical intervention: outcome to airflow and olfaction.
• Pharmacokinetics and pharmacodynamics of nonsteroidal androgen receptor ligands.
• Progress in development of liver fluke vaccines.
• Proposal raises bones of contention.
• Serological response to hepatitis E virus genotype 3 infection: IgG quantitation, avidity, and IgM response.
• Stereoselective reductase-catalysed deoxygenation of sulfoxides in aerobic and anaerobic bacteria.
• The Levonorgestrel-releasing Intrauterine System: An Updated Review of the Contraceptive and Noncontraceptive Uses.
• Treating anemia of chronic kidney disease in the primary care setting: cardiovascular outcomes and management recommendations.
• US university finds use for Air Force research reactor.
• US warms to carbon sequestration research.
• Veterinary poisons information service.