Ontology highlight
ABSTRACT:
SUBMITTER: Ojo KK
PROVIDER: S-EPMC2896873 | biostudies-literature | 2010 May
REPOSITORIES: biostudies-literature
Ojo Kayode K KK Larson Eric T ET Keyloun Katelyn R KR Castaneda Lisa J LJ Derocher Amy E AE Inampudi Krishna K KK Kim Jessica E JE Arakaki Tracy L TL Murphy Ryan C RC Zhang Li L Napuli Alberto J AJ Maly Dustin J DJ Verlinde Christophe L M J CL Buckner Frederick S FS Parsons Marilyn M Hol Wim G J WG Merritt Ethan A EA Van Voorhis Wesley C WC
Nature structural & molecular biology 20100502 5
New drugs are needed to treat toxoplasmosis. Toxoplasma gondii calcium-dependent protein kinases (TgCDPKs) are attractive targets because they are absent in mammals. We show that TgCDPK1 is inhibited by low nanomolar levels of bumped kinase inhibitors (BKIs), compounds inactive against mammalian kinases. Cocrystal structures of TgCDPK1 with BKIs confirm that the structural basis for selectivity is due to the unique glycine gatekeeper residue in the ATP-binding site. We show that BKIs interfere w ...[more]