2PMO
Crystal structure of PfPK7 in complex with hymenialdisine
Summary for 2PMO
| Entry DOI | 10.2210/pdb2pmo/pdb |
| Descriptor | Ser/Thr protein kinase, 4-(5-AMINO-4-OXO-4H-PYRAZOL-3-YL)-2-BROMO-4,5,6,7-TETRAHYDRO-3AH-PYRROLO[2,3-C]AZEPIN-8-ONE (3 entities in total) |
| Functional Keywords | ser/thr protein kinase; plasmodium falciparum; transferase; phosphorylation, transferase |
| Biological source | Plasmodium falciparum (malaria parasite P. falciparum) |
| Total number of polymer chains | 1 |
| Total formula weight | 41758.73 |
| Authors | Merckx, A.,Echalier, A.,Noble, M.,Endicott, J. (deposition date: 2007-04-23, release date: 2008-01-22, Last modification date: 2023-08-30) |
| Primary citation | Merckx, A.,Echalier, A.,Langford, K.,Sicard, A.,Langsley, G.,Joore, J.,Doerig, C.,Noble, M.,Endicott, J. Structures of P. falciparum protein kinase 7 identify an activation motif and leads for inhibitor design. Structure, 16:228-238, 2008 Cited by PubMed Abstract: 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. PubMed: 18275814DOI: 10.1016/j.str.2007.11.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
Download full validation report
