4M84

Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1455

Summary for 4M84

• Entry DOI: 10.2210/pdb4m84/pdb
• Descriptor: Calmodulin-domain protein kinase 1, 5-amino-1-tert-butyl-3-(quinolin-2-yl)-1H-pyrazole-4-carboxamide (3 entities in total)
• Functional Keywords: serine/threonine protein kinase, transferase, calcium-binding, atp-binding, bumped kinase inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Toxoplasma gondii
• Total number of polymer chains: 1
• Total formula weight: 55536.28

Authors

Merritt, E.A. (deposition date: 2013-08-12, release date: 2013-10-02, Last modification date: 2023-09-20)

Primary citation

Zhang, Z.,Ojo, K.K.,Vidadala, R.,Huang, W.,Geiger, J.A.,Scheele, S.,Choi, R.,Reid, M.C.,Keyloun, K.R.,Rivas, K.,Siddaramaiah, L.K.,Comess, K.M.,Robinson, K.P.,Merta, P.J.,Kifle, L.,Hol, W.G.,Parsons, M.,Merritt, E.A.,Maly, D.J.,Verlinde, C.L.,Van Voorhis, W.C.,Fan, E.
Potent and selective inhibitors of CDPK1 from T. gondii and C. parvum based on a 5-aminopyrazole-4-carboxamide scaffold.
ACS Med Chem Lett, 5:40-44, 2014

PubMed Abstract: 5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known "bumped kinase inhibitor" to create selective inhibitors of calcium-dependent protein kinase-1 from both and . Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in cell proliferation assays and were shown to be non-toxic to mammalian cells.

PubMed: 24494061
DOI: 10.1021/ml400315s

Experimental method

X-RAY DIFFRACTION (1.998 Å)