Enzymatic properties of the lactate dehydrogenase enzyme from Plasmodium falciparum

Deborah K. Shoemark, Matthew J. Cliff, Richard B. Sessions, Anthony R. Clarke

Research output: Contribution to journalArticlepeer-review

Abstract

The lactate dehydrogenase enzyme from Plasmodium falciparum (PfLDH) is a target for antimalarial compounds owing to structural and functional differences from the human isozymes. The plasmodial enzyme possesses a five-residue insertion in the substrate-specificity loop and exhibits less marked substrate inhibition than its mammalian counterparts. Here we provide a comprehensive kinetic analysis of the enzyme by steady-state and transient kinetic methods. The mechanism deduced by product inhibition studies proves that PfLDH shares a common mechanism with the human LDHs, that of an ordered sequential bireactant system with coenzyme binding first. Transient kinetic analysis reveals that the major rate-limiting step is the closure of the substrate-specificity loop prior to hydride transfer, in line with other LDHs. The five-residue insertion in this loop markedly increases substrate specificity compared with the human muscle and heart isoforms.

Original languageEnglish
Pages (from-to)2738-2748
Number of pages11
JournalFEBS Journal
Volume274
Issue number11
Early online date25 Apr 2007
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Kinetic
  • Lactate dehydrogenase
  • Malaria
  • Mechanism
  • Plasmodium falciparum

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