1k9a
Crystal structure analysis of full-length carboxyl-terminal Src kinase at 2.5 A resolution
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OverviewOverview
The carboxyl-terminal Src kinase (Csk) is an indispensable negative, regulator for the Src family tyrosine kinases (SFKs) that play pivotal, roles in various cell signalings. To understand the molecular basis of the, Csk-mediated regulation of SFKs, we elucidated the crystal structure of, full-length Csk. The Csk crystal consists of six molecules classified as, active or inactive states according to the coordinations of catalytic, residues. Csk assembles the SH2 and SH3 domains differently from inactive, SFKs, and their binding pockets are oriented outward enabling the, intermolecular interaction. In active molecules, the SH2-kinase and, SH2-SH3 linkers are tightly stuck to the N-lobe of the kinase domain to, stabilize the active conformation, and there is a direct linkage between, the SH2 and the kinase domains. In inactive molecules, the SH2 domains are, rotated destroying the linkage to the kinase domain. Cross-correlation, matrices for the active molecules reveal that the SH2 domain and the, N-lobe of the kinase domain move as a unit. These observations suggest, that Csk can be regulated through coupling of the SH2 and kinase domains, and that Csk provides a novel built-in activation mechanism for, cytoplasmic tyrosine kinases.
About this StructureAbout this Structure
1K9A is a Single protein structure of sequence from Rattus norvegicus. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
ReferenceReference
Structure of the carboxyl-terminal Src kinase, Csk., Ogawa A, Takayama Y, Sakai H, Chong KT, Takeuchi S, Nakagawa A, Nada S, Okada M, Tsukihara T, J Biol Chem. 2002 Apr 26;277(17):14351-4. Epub 2002 Mar 7. PMID:11884384
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