Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with inhibitor UNC569

Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia.

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 C52

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

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

tyrosine kinase, acute lymphoblastic leukemia, rational structure-based drug design, TRANSFERASE-TRANSFERASE INHIBITOR complex

SEELQNKLEDVVIDRNLLILGKILGEGEFGSVMEGNLKQEDGTSLKVAVKTMKLDNSSQREIEEFLSEAACMKDFSHPNV
IRLLGVCIEMSSQGIPKPMVILPFMKYGDLHTYLLYSRLETGPKHIPLQTLLKFMVDIALGMEYLSNRNFLHRDLAARNC
MLRDDMTVCVADFGLSKKIYSGDYYRQGRIAKMPVKWIAIESLADRVYTSKSDVWAFGVTMWEIATRGMTPYPGVQNHEM
YDYLLHGHRLKQPEDCLDELYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDV