2abl
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SH3-SH2 DOMAIN FRAGMENT OF HUMAN BCR-ABL TYROSINE KINASE
OverviewOverview
BACKGROUND. The Abl nonreceptor tyrosine kinase is implicated in a range, of cellular processes and its transforming variants are involved in human, leukemias. The N-terminal regulatory region of the Abl protein contains, Src homology domains SH2 and SH3 which have been shown to be important for, the regulation of its activity in vivo. These domains are often found, together in the same protein and biochemical data suggest that the, functions of one domain can be influenced by the other. RESULTS. We have, determined the crystal structure of the Abl regulatory region containing, the SH3 and SH2 domains. In general, the individual domains are very, similar to those of previously solved structures, although the Abl SH2, domain contains a loop which is extended so that one side of the resulting, phosphotyrosine-binding pocket is open. In our structure the protein, exists as a monomer with no intermolecular contacts to which a biological, function may be attributed. However, there is a significant intramolecular, contact between a loop of the SH3 domain and the extended loop of the SH2, domain. This contact surface includes the SH2 loop segment that is, responsible for binding the phosphate moiety of phosphotyrosine-containing, proteins and is therefore critical for orienting peptide interactions., CONCLUSIONS. The crystal structure of the composite Abl SH3-SH2 domain, provides the first indication of how SH2 and SH3 domains communicate with, each other within the same molecule and why the presence of one directly, influences the activity of the other. This is the first clear evidence, that these two domains are in contact with each other. The results suggest, that this direct interaction between the two domains may affect the ligand, binding properties of the SH2 domain, thus providing an explanation for, biochemical and functional data concerning the Bcr-Abl kinase.
DiseaseDisease
Known diseases associated with this structure: Leukemia, Philadelphia chromosome-positive, resistant to imatinib OMIM:[189980]
About this StructureAbout this Structure
2ABL is a Single protein structure of sequence from Homo sapiens. 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
Intramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism., Nam HJ, Haser WG, Roberts TM, Frederick CA, Structure. 1996 Sep 15;4(9):1105-14. PMID:8805596
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