Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with Bumped Kinase Inhibitor, RM-1-89

Multiple determinants for selective inhibition of apicomplexan calcium-dependent protein kinase CDPK1.

Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.

Discovery of Potent and Selective Inhibitors of Calcium-Dependent Protein Kinase 1 (CDPK1) from C. parvum and T. gondii.

1.00 degrees, 4.0 sec, detector distance 300.00 mm

side scattering I-beam bent single crystal; asymmetric cut 4.965 deg.

Calmodulin-domain protein kinase, putative

GPGSMMDHLHATPGMFVQHSTAIFSDRYKGQRVLGKGSFGEVILCKDKITGQECAVKVISKRQVKQKTDKESLLREVQLL
KQLDHPNIMKLYEFFEDKGYFYLVGEVYTGGELFDEIISRKRFSEVDAARIIRQVLSGITYMHKNKIVHRDLKPENLLLE
SKSKDANIRIIDFGLSTHFEASKKMKDKIGTAYYIAPEVLHGTYDEKCDVWSTGVILYILLSGCPPFNGANEYDILKKVE
KGKYTFELPQWKKVSESAKDLIRKMLTYVPSMRISARDALDHEWIQTYTKEQISVDVPSLDNAILNIRQFQGTQKLAQAA
LLYMGSKLTSQDETKELTAIFHKMDKNGDGQLDRAELIEGYKELMRMKGQDASMLDASAVEHEVDQVLDAVDFDKNGYIE
YSEFVTVAMDRKTLLSRERLERAFRMFDSDNSGKISSTELATIFGVSDVDSETWKSVLSEVDKNNDGEVDFDEFQQMLLK
LCGN

residues 1-29 were replaced with a cleavable His-tag plus linker during cloning; tag was cleaved prior to crystallization

26% PEG 3350, 0.275 M ammonium citrate, 5 mM DTT, 2.3 mM RM-1-89; mother liquor supplemented with 10% ethylene glycol prior to freezing in LN2, pH 7.0, vapor diffusion, sitting drop, temperature 298K

homolog from C. parvum in complex with RM-1-95 and calcium

homolog from C. parvum in complex with NM-PP1 and calcium

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS; U VALUES: WITH TLS ADDED

serine/threonine protein kinase, transferase, calcium-binding, ATP-binding, calmodulin, EF hand, bumped kinase inhibitor, transferase-transferase inhibitor complex

DHLHATPGMFVQHSTAIFSDRYKGQRVLGKGSFGEVILCKDKITGQECAVKVISKRQVKQKTDKESLLREVQLLKQLDHP
NIMKLYEFFEDKGYFYLVGEVYTGGELFDEIISRKRFSEVDAARIIRQVLSGITYMHKNKIVHRDLKPENLLLESKSKDA
NIRIIDFGLSTHFEASKKMKDKIGTAYYIAPEVLHGTYDEKCDVWSTGVILYILLSGCPPFNGANEYDILKKVEKGKYTF
ELPQWKKVSESAKDLIRKMLTYVPSMRISARDALDHEWIQTYTKEQISVDVPSLDNAILNIRQFQGTQKLAQAALLYMGS
KLTSQDETKELTAIFHKMDKNGDGQLDRAELIEGYKELMRMKGQDASMLDASAVEHEVDQVLDAVDFDKNGYIEYSEFVT
VAMDRKTLLSRERLERAFRMFDSDNSGKISSTELATIFGVSDVDSETWKSVLSEVDKNNDGEVDFDEFQQMLLKLCGN