Crystal structure of the L317I mutant of the C-src tyrosine kinase domain complexed with dasatinib

A single amino-acid dictates the dynamics of the switch between active and inactive C-src conformation

c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty.

Small molecule recognition of c-Src via the Imatinib-binding conformation.

Proto-oncogene tyrosine-protein kinase Src

Proto-oncogene c-Src, pp60c-src, p60-Src

GHMQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKIRHEKLVQLYA
VVSEEPIYIVTEYMSKGSLLDFLKGEMGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGL
ARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPEC
PESLHDLMCQCWRKDPEERPTFEYLQAFLEDYFTSTEPQYQPGENL

7mg/ml protein, 0.25mM dasatinib, 0.1M MES, 0.2M sodium acetate, 4% Glycerol, 12% PEG 4000, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 287K

crystal structure of the L317I mutant of the chicken c-Src tyrosine kinase domain

crystal structure of the L317I mutant of the chicken c-Src tyrosine kinase domain complexed with imatinib

crystal structure of the L317I mutant of the c-Src tyrosine kinase domain complexed with pyrazolopyrimidine 5

Kinase domain of cSrc in complex with Dasatinib

C-SRC L317I MUTANT, TYROSINE KINASE, TRANSFERASE, DASATINIB

QTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVS
EEPIYIVTEYMSKGSLLDFLKGEMGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARL
IEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPES
LHDLMCQCWRKDPEERPTFEYLQAFLEDYFTSTEPQYQPGENL