2PMN

Crystal structure of PfPK7 in complex with an ATP-site inhibitor

2PMN の概要

• エントリーDOI: 10.2210/pdb2pmn/pdb
• 分子名称: Ser/Thr protein kinase, putative, 4-(6-{[(1S)-1-(HYDROXYMETHYL)-2-METHYLPROPYL]AMINO}IMIDAZO[1,2-B]PYRIDAZIN-3-YL)BENZONITRILE (3 entities in total)
• 機能のキーワード: ser/thr protein kinase; plasmodium falciparum; transferase; phosphorylation, transferase
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41755.97

構造登録者

Merckx, A.,Echalier, A.,Noble, M.,Endicott, J. (登録日: 2007-04-23, 公開日: 2008-01-22, 最終更新日: 2023-08-30)

主引用文献

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

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: 18275814
DOI: 10.1016/j.str.2007.11.014

実験手法

X-RAY DIFFRACTION (2.8 Å)