Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-1-12
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-10320401, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-10395732, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-10460171, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-10479734, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-10790433, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-10801129, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-10944387, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-11052681, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-11390365, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-11604523, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-11884384, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-12522303, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-12686554, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-1379696, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-14566052, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-14980511, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-15312765, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-15502869, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-15683240, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-15939018, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-16002086, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-16213199, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-16243715, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-1722201, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-2610349, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-5289868, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-7683130, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-7883800, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-8251932, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-8520220, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-8855443, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-9434895, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-9442882, http://linkedlifedata.com/resource/pubmed/commentcorrection/17137590-9601030
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
365
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1460-8
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.
pubmed:affiliation
Department of Chemistry & Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural