2src
From Proteopedia
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|PDB= 2src |SIZE=350|CAPTION= <scene name='initialview01'>2src</scene>, resolution 1.5Å | |PDB= 2src |SIZE=350|CAPTION= <scene name='initialview01'>2src</scene>, resolution 1.5Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER'>ANP</scene> | + | |LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://www.ebi.ac.uk/pdbsum/2src PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB]</span> | ||
}} | }} | ||
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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 exposure and phosphorylation of Tyr-416. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190090 190090]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Lei, M.]] | [[Category: Lei, M.]] | ||
[[Category: Xu, W.]] | [[Category: Xu, W.]] | ||
| - | [[Category: ANP]] | ||
[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
[[Category: phosphotransferase]] | [[Category: phosphotransferase]] | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:03:26 2008'' |
Revision as of 02:03, 31 March 2008
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| , resolution 1.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP
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.
About this Structure
2SRC is a Single protein structure of sequence from Homo sapiens. The following pages contain interesting information on the relation of 2SRC with [Ubiquitin]. 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 Mar 31 05:03:26 2008
