3i7b | pdb_00003i7b

Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with bumped kinase inhibitor NM-PP1

spinqualitylabelsall models 3i7b, resolution 1.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3i7b is a 1 chain structure with sequence from Toxoplasma gondii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.988Å Ligands: BK1, DMS, EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9BJF5_TOXGO Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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 with an early step in T. gondii infection of human cells in culture. Furthermore, we show that TgCDPK1 is the in vivo target of BKIs because T. gondii expressing a glycine to methionine gatekeeper mutant enzyme show significantly decreased sensitivity to BKIs. Thus, design of selective TgCDPK1 inhibitors with low host toxicity may be achievable. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.,Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, Derocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy RC, Zhang L, Napuli AJ, Maly DJ, Verlinde CL, Buckner FS, Parsons M, Hol WG, Merritt EA, Van Voorhis WC Nat Struct Mol Biol. 2010 May;17(5):602-7. Epub 2010 May 2. PMID:20436472 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Calcium-dependent protein kinase

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