2pmo
From Proteopedia
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| , resolution 2.90Å | |||||||
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| Sites: | |||||||
| Ligands: | |||||||
| Gene: | PFB0605w (Plasmodium falciparum) | ||||||
| Domains: | S_TKc, S_TKc | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of PfPK7 in complex with hymenialdisine
Overview
Malaria is a major threat to world health. The identification of parasite targets for drug development is a priority and parasitic protein kinases suggest themselves as suitable targets as many display profound structural and functional divergences from their host counterparts. In this paper, we describe the structure of the orphan protein kinase, Plasmodium falciparum protein kinase 7 (PFPK7). Several Plasmodium protein kinases contain extensive insertions, and the structure of PFPK7 reveals how these may be accommodated as excursions from the canonical eukaryotic protein kinase fold. The constitutively active conformation of PFPK7 is stabilized by a structural motif in which the role of the conserved phosphorylated residue that assists in structuring the activation loop of many protein kinases is played by an arginine residue. We identify two series of PFPK7 ATP-competitive inhibitors and suggest further developments for the design of selective and potent PFPK7 lead compounds as potential antimalarials.
About this Structure
2PMO is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
Structures of P. falciparum protein kinase 7 identify an activation motif and leads for inhibitor design., Merckx A, Echalier A, Langford K, Sicard A, Langsley G, Joore J, Doerig C, Noble M, Endicott J, Structure. 2008 Feb;16(2):228-38. PMID:18275814
Page seeded by OCA on Wed Apr 2 11:31:49 2008
