Crystals of peptide deformylase from Plasmodium falciparum reveal critical characteristics of the active site for drug design.
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Kumar A, Nguyen KT, Srivathsan S, Ornstein B, Turley S, Hirsh I, Pei D, Hol WG
Crystals of peptide deformylase from Plasmodium falciparum reveal critical characteristics of the active site for drug design.
Structure. 2002 Mar;10(3):357-67.
- PubMed ID
- 12005434 [ View in PubMed]
- Abstract
Peptide deformylase catalyzes the deformylation reaction of the amino terminal fMet residue of newly synthesized proteins in bacteria, and most likely in Plasmodium falciparum, and has therefore been identified as a potential antibacterial and antimalarial drug target. The structure of P. falciparum peptide deformylase, determined at 2.8 A resolution with ten subunits per asymmetric unit, is similar to the bacterial enzyme with the residues involved in catalysis, the position of the bound metal ion, and a catalytically important water structurally conserved between the two enzymes. However, critical differences in the substrate binding region explain the poor affinity of E. coli deformylase inhibitors and substrates toward the Plasmodium enzyme. The Plasmodium structure serves as a guide for designing novel antimalarials.