title: Structural basis for the decarboxylation of orotidine 5'-monophosphate (OMP) by Plasmodium falciparum OMP decarboxylase.
abstract: Orotidine 5'-monophoshate decarboxylase (OMPDC) catalyses the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP). Here, we report the X-ray analysis of apo, substrate or product-complex forms of OMPDC from Plasmodium falciparum (PfOMPDC) at 2.7, 2.65 and 2.65 A, respectively. The structural analysis provides the substrate recognition mechanism with dynamic structural changes, as well as the rearrangement of the hydrogen bond array at the active site. The structural basis of substrate or product binding to PfOMPDC will help to uncover the decarboxylation mechanism and facilitate structure-based optimization of antimalarial drugs.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tokuoka
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kusakari
authors.forename: Sudaratana R
authors.initials: SR
authors.lastname: Krungkrai
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsumura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kai
authors.forename: Jerapan
authors.initials: J
authors.lastname: Krungkrai
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001051:Apoenzymes / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003653:Decarboxylation; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000737:chemistry* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D001051:Apoenzymes; D015800:Protozoan Proteins; C005417:orotidylic acid; D014542:Uridine Monophosphate; D009964:Orotidine-5'-Phosphate Decarboxylase; D008239:Lysine