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Re‐refinement of Plasmodium falciparum orotidine 5′‐monophosphate decarboxylase provides a clearer picture of an important malarial drug target
Author(s) -
Novak Walter R. P.,
West Korbin H. J.,
Kirkman Lucy M. D.,
Brandt Gabriel S.
Publication year - 2018
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x18010610
Subject(s) - protein data bank (rcsb pdb) , plasmodium falciparum , stereochemistry , chemistry , enzyme , substrate (aquarium) , drug , ligand (biochemistry) , computational biology , active site , biochemistry , biology , combinatorial chemistry , malaria , pharmacology , receptor , immunology , ecology
The development of antimalarial drugs remains a public health priority, and the orotidine 5′‐monophosphate decarboxylase from Plasmodium falciparum (PfOMPDC) has great potential as a drug target. The crystallization of PfOMPDC with substrate bound represents an important advance for structure‐based drug‐design efforts [Tokuoka et al. (2008), J. Biochem. 143 , 69–78]. The complex of the enzyme bound to the substrate OMP (PDB entry 2za1) would be of particular utility in this regard. However, re‐refinement of this structure of the Michaelis complex shows that the bound ligand is the product rather than the substrate. Here, the re‐refinement of a set of three structures, the apo enzyme and two versions of the product‐bound form (PDB entries 2za1, 2za2 and 2za3), is reported. The improved geometry and fit of these structures to the observed electron density will enhance their utility in antimalarial drug design.