A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Abstract Text:

Jamie E Mills,Paul C Whitford,Jennifer Shaffer,Jose N Onuchic,Joseph A Adams,Patricia A Jennings,

The SH2 domain of the C-terminal Src kinase [Csk] contains a unique disulfide bond that is not present in other known SH2 domains. To investigate whether this unusual disulfide bond serves a novel function, the effects of disulfide bond formation on catalytic activity of the full-length protein and on the structure of the SH2 domain were investigated. The kinase activity of full-length Csk decreases by an order of magnitude upon formation of the disulfide bond in the distal SH2 domain. NMR spectra of the fully oxidized and fully reduced SH2 domains exhibit similar chemical shift patterns and are indicative of similar, well-defined tertiary structures. The solvent-accessible disulfide bond in the isolated SH2 domain is highly stable and far from the small lobe of the kinase domain. However, reduction of this bond results in chemical shift changes of resonances that map to a cluster of residues that extend from the disulfide bond across the molecule to a surface that is in direct contact with the small lobe of the kinase domain in the intact molecule. Normal mode analyses and molecular dynamics calculations suggest that disulfide bond formation has large effects on residues within the kinase domain, most notably within the active-site cleft. Overall, the data indicate that reversible cross-linking of two cysteine residues in the SH2 domain greatly impacts catalytic function and interdomain communication in Csk.

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Publishing Authors By Initials

JE Mills,PC Whitford,J Shaffer,JN Onuchic,JA Adams,PA Jennings,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary: protein interaction domains and motifs: src homology domains research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary: protein interaction domains and motifs: src homology domains research

PUBMED ID PMID:

MEDLINE DATE:

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of molecular biology

VOLUME: 365

Page Numbers: 1460-8

Journal Abbreviation: J. Mol. Biol.

ISSN: 0022-2836

DAY: 26

MONTH: 10

YEAR: 2006

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985088

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Keywords Mesh Terms:

KEYWORDS: src Homology Domains

MESH TERMS: metabolism

Chemical & Substance for Abstract: A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity. Information

Substance Name: protein-tyrosine kinase c-src

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.

AFFILIATION: Department of Chemistry & Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA.

Country: England

AGENCY: United States NIGMS

GRANT: T32 GM 08326

ACRONYM: GM

MEDLINETA: J Mol Biol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity Related Publications

• A Highly Stereoselective TMSOTf-Mediated Catalytic Carbocupration of Alkynoates.
• A bacteriologic survey of the reproductive tract of infertile cows.
• A case of an isolated gastric variceal bleed secondary to a pancreatic neuroendocrine tumour.
• A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.
• Amino acid sequence of a ferredoxin from Chlorobium thiosulfatophilum strain Tassajara, a photosynthetic green sulfur bacterium.
• An advanced solventless column test for capillary GC columns.
• Brucellosis: Consideration of Its Epidemiology, Diagnosis and Control.
• Characterization of the OxyR regulon of Neisseria gonorrhoeae.
• Chlorophyll ring deformation modulates Qy electronic energy in chlorophyll-protein complexes and generates spectral forms.
• Data briefing. Efficiency efforts begin to pay off.
• Growth and structure of surface-initiated poly(n-alkylnorbornene) films.
• Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression.
• Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro.
• Kinetics of pH response for copolymer films with dilute carboxylate functionality.
• Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons.
• MR cholangiopancreatography in children: feasibility, safety, and initial experience.
• Maximum common subgraph: some upper bound and lower bound results.
• MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone.
• New directions in nursing home ethics.
• Peritoneal dialysis catheters: laparoscopic versus traditional placement techniques and outcomes.
• Phase variable type III restriction-modification systems of host-adapted bacterial pathogens.
• Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy.
• Public Health Engineering: The Practical Application of Milk Control.
• Resistance to arranged marriage among Nubian youth: ideology and changing times.
• Secretory signal sequence non-optimal codons are required for expression and export of beta-lactamase.
• The most wonderful organ-not!
• The rough energy landscape of superfolder GFP is linked to the chromophore.
• Thromboembolism; prophylaxis and treatment.
• Transferred NOE and saturation transfer difference NMR studies of novobiocin binding to EnvZ suggest binding mode similar to DNA gyrase.
• [2]Pseudorotaxane and [2]rotaxane molecular shuttles: self-assembly through second-sphere coordination of thiocyanate ligands.