2SRC

CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP

Summary for 2SRC

• Entry DOI: 10.2210/pdb2src/pdb
• Descriptor: TYROSINE-PROTEIN KINASE SRC, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: src, tyrosine-protein kinase, phosphorylation, sh2, sh3, phosphotyrosine, proto-oncogene, phosphotransferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane: P12931
• Total number of polymer chains: 1
• Total formula weight: 52215.77

Authors

Xu, W.,Doshi, A.,Lei, M.,Eck, M.J.,Harrison, S.C. (deposition date: 1998-12-29, release date: 1999-07-22, Last modification date: 2024-10-30)

Primary citation

Xu, W.,Doshi, A.,Lei, M.,Eck, M.J.,Harrison, S.C.
Crystal structures of c-Src reveal features of its autoinhibitory mechanism.
Mol.Cell, 3:629-638, 1999

PubMed Abstract: 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.

PubMed: 10360179
DOI: 10.1016/S1097-2765(00)80356-1

Experimental method

X-RAY DIFFRACTION (1.5 Å)