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Journal of Biochemistry Advance Access originally published online on November 1, 2007
Journal of Biochemistry 2008 143(1):69-78; doi:10.1093/jb/mvm193
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© 2007 The Japanese Biochemical Society.

Structural Basis for the Decarboxylation of Orotidine 5'-Monophosphate (OMP) by Plasmodium Falciparum OMP Decarboxylase{dagger}

Keiji Tokuoka1, Yukiko Kusakari1, Sudaratana R. Krungkrai2,3, Hiroyoshi Matsumura1, Yasushi Kai1, Jerapan Krungkrai4, Toshihiro Horii2 and Tsuyoshi Inoue1,*

1Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871; 2Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; 3Unit of Biochemistry, Department of Medical Science, Faculty of Science, Rangsit University, Patumthani 12000; and 4Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Bangkok 10330, Thailand

*To whom correspondence should be addressed. Tel: +81-6-6879-7410, Fax: +81-6-6879-7409, E-mail: inouet{at}chem.eng.osaka-u.ac.jp

Received August 6, 2007; Accepted October 2, 2007


  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 Å, 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.

Key Words: apo form, OMP-complex, orotidine 5'-monophoshate decarboxylase, structural comparison, UMP-complex, x-ray structural analysis

Abbreviations: OMP, orotidine 5'-monophosphate; OMPDC, OMP decarboxylase; PfOMPDC, OMPDC from Plasmodium falciparum; OPRT, orotate phosphoribosyltransferase; SDS–PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis

{dagger}Coordinates have been deposited in the Protein Data Bank (accession codes 2ZA2, 2ZA1 and 2ZA3 for the apo form, and OMP- or UMP-complex of PfOMPDC, respectively).


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