Structural basis for the decarboxylation of orotidine 5'-monophosphate (OMP) by Plasmodium falciparum OMP decarboxylase.
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.
Tokuoka
Keiji
K
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Kusakari
Yukiko
Y
Krungkrai
Sudaratana R
SR
Matsumura
Hiroyoshi
H
Kai
Yasushi
Y
Krungkrai
Jerapan
J
Horii
Toshihiro
T
Inoue
Tsuyoshi
T
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
D001051:Apoenzymes; D015800:Protozoan Proteins; C005417:orotidylic acid; D014542:Uridine Monophosphate; D009964:Orotidine-5'-Phosphate Decarboxylase; D008239:Lysine