title: An improved crystal form of Plasmodium falciparum peptide deformylase.
abstract: An altered version of peptide deformylase from Plasmodium falciparum (PfPDF), the organism that causes the most devastating form of malaria, has been cocrystallized with a synthesized inhibitor that has submicromolar affinity for its target protein. The structure is solved at 2.2 A resolution, an improvement over the 2.8 A resolution achieved during the structural determination of unliganded PfPDF. This represents the successful outcome of modifying the protein construct in order to overcome adverse crystal contacts and other problems encountered in the study of unliganded PfPDF. Two molecules of PfPDF are found in the asymmetric unit of the current structure. The active site of each monomer of PfPDF is occupied by a proteolyzed fragment of the tripeptide-like inhibitor. Unexpectedly, each PfPDF subunit is associated with two nearly complete molecules of the inhibitor, found at a protein-protein interface. This is the first structure of a eukaryotic PDF protein, a potential drug target, in complex with a ligand.
authors.affiliation: University of Washington, Seattle, Washington 98195, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Robien
authors.forename: Kiet T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kumar
authors.forename: Irwin
authors.initials: I
authors.lastname: Hirsh
authors.forename: Stewart
authors.initials: S
authors.lastname: Turley
authors.forename: Dehua
authors.initials: D
authors.lastname: Pei
authors.forename: Wim G J
authors.initials: WG
authors.lastname: Hol
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000201:enzymology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D000581:Amidohydrolases; C084507:peptide deformylase