Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with inhibitor UNC1817

Discovery of Mer specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis.

Proto-oncogene c-Mer, Receptor tyrosine kinase MerTK

MGSSHHHHHHSSGLVPRGSEELQNKLEDVVIDRNLLILGKILGEGEFGSVMEGNLKQEDGTSLKVAVKTMKLDNSSQREI
EEFLSEAACMKDFSHPNVIRLLGVCIEMSSQGIPKPMVILPFMKYGDLHTYLLYSRLETGPKHIPLQTLLKFMVDIALGM
EYLSNRNFLHRDLAARNCMLRDDMTVCVADFGLSKKIYSGDYYRQGRIAKMPVKWIAIESLADRVYTSKSDVWAFGVTMW
EIATRGMTPYPGVQNHEMYDYLLHGHRLKQPEDCLDELYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDV

Protein: 32.5 mg/mL in 20 mM Tris pH 8.0, 500mM sodium chloride, 2mM beta-mercaptoethanol, incubated with inhibitor (2.5 mM final concentration) overnight, mixed 1:1 with crystallization solution (27-33% (v/v) Peg400, 200 mM magnesium chloride, 100 mM Tris pH 8.5), VAPOR DIFFUSION, SITTING DROP, temperature 288K

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF THE PROTO-ONCOGENE TYROSINE-PROTEIN KINASE MER IN COMPLEX WITH INHIBITOR UNC1917

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF THE PROTO-ONCOGENE TYROSINE-PROTEIN KINASE MER IN COMPLEX WITH INHIBITOR UNC569

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF THE PROTO-ONCOGENE TYROSINE-PROTEIN KINASE MER IN COMPLEX WITH ADP

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF THE PROTO-ONCOGENE TYROSINE-PROTEIN KINASE MER IN COMPLEX WITH INHIBITOR C52

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF THE PROTO-ONCOGENE TYROSINE-PROTEIN KINASE MER

TYROSINE KINASE, ACUTE LYMPHOBLASTIC LEUKEMIA, RATIONAL STRUCTURE-BASED DRUG DESIGN, TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX

SEELQNKLEDVVIDRNLLILGKILGEGEFGSVMEGNLKQEDGTSLKVAVKTMKLDNSSQREIEEFLSEAACMKDFSHPNV
IRLLGVCIEMSSQGIPKPMVILPFMKYGDLHTYLLYSRLETGPKHIPLQTLLKFMVDIALGMEYLSNRNFLHRDLAARNC
MLRDDMTVCVADFGLSKKIYSGDYYRQGRIAKMPVKWIAIESLADRVYTSKSDVWAFGVTMWEIATRGMTPYPGVQNHEM
YDYLLHGHRLKQPEDCLDELYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDV