2src
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Src family kinases are maintained in an assembled, inactive conformation, by intramolecular interactions of their SH2 and SH3 domains. Full, catalytic activity requires release of these restraints as well as, phosphorylation of Tyr-416 in the activation loop. In previous structures, of inactive Src kinases, Tyr-416 and flanking residues are disordered. We, report here four additional c-Src structures in which this segment adopts, an ordered but inhibitory conformation. The ordered activation loop forms, an alpha helix that stabilizes the inactive conformation of the kinase, domain, blocks the peptide substrate-binding site, and prevents Tyr-416, phosphorylation. Disassembly of the regulatory domains, induced by SH2 or, SH3 ligands, or by dephosphorylation of Tyr-527, could lead to . | + | Src family kinases are maintained in an assembled, inactive conformation, by intramolecular interactions of their SH2 and SH3 domains. Full, catalytic activity requires release of these restraints as well as, phosphorylation of Tyr-416 in the activation loop. In previous structures, of inactive Src kinases, Tyr-416 and flanking residues are disordered. We, report here four additional c-Src structures in which this segment adopts, an ordered but inhibitory conformation. The ordered activation loop forms, an alpha helix that stabilizes the inactive conformation of the kinase, domain, blocks the peptide substrate-binding site, and prevents Tyr-416, phosphorylation. Disassembly of the regulatory domains, induced by SH2 or, SH3 ligands, or by dephosphorylation of Tyr-527, could lead to exposure, and phosphorylation of Tyr-416. |
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Colon cancer, advanced OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190090 190090]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2SRC is a | + | 2SRC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ANP as [http://en.wikipedia.org/wiki/ligand ligand]. The following pages contain interesting information on the relation of 2SRC with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb60_1.html Ubiquitin]]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Src Tyrosine Kinase]] | [[Category: Src Tyrosine Kinase]] | ||
| + | [[Category: Transferase]] | ||
[[Category: Ubiquitin]] | [[Category: Ubiquitin]] | ||
[[Category: Doshi, A.]] | [[Category: Doshi, A.]] | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:38:11 2007'' |
Revision as of 21:31, 12 November 2007
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CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP
Contents |
Overview
Src family kinases are maintained in an assembled, inactive conformation, by intramolecular interactions of their SH2 and SH3 domains. Full, catalytic activity requires release of these restraints as well as, phosphorylation of Tyr-416 in the activation loop. In previous structures, of inactive Src kinases, Tyr-416 and flanking residues are disordered. We, report here four additional c-Src structures in which this segment adopts, an ordered but inhibitory conformation. The ordered activation loop forms, an alpha helix that stabilizes the inactive conformation of the kinase, domain, blocks the peptide substrate-binding site, and prevents Tyr-416, phosphorylation. Disassembly of the regulatory domains, induced by SH2 or, SH3 ligands, or by dephosphorylation of Tyr-527, could lead to exposure, and phosphorylation of Tyr-416.
Disease
Known disease associated with this structure: Colon cancer, advanced OMIM:[190090]
About this Structure
2SRC is a Single protein structure of sequence from Homo sapiens with ANP as ligand. The following pages contain interesting information on the relation of 2SRC with [Ubiquitin]. 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.
Reference
Crystal structures of c-Src reveal features of its autoinhibitory mechanism., Xu W, Doshi A, Lei M, Eck MJ, Harrison SC, Mol Cell. 1999 May;3(5):629-38. PMID:10360179
Page seeded by OCA on Mon Nov 12 23:38:11 2007
Categories: Homo sapiens | Single protein | Src Tyrosine Kinase | Transferase | Ubiquitin | Doshi, A. | Eck, M.J. | Harrison, S.C. | Lei, M. | Xu, W. | ANP | Phosphorylation | Phosphotransferase | Phosphotyrosine | Proto-oncogene | Sh2 | Sh3 | Src | Tyrosine-protein kinase
