Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum

FEBS Lett. 2013 Dec 11;587(24):3968-72. doi: 10.1016/j.febslet.2013.10.029. Epub 2013 Nov 1.


Terpenoid precursor biosynthesis occurs in human and many pathogenic organisms via the mevalonate and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways, respectively. We determined the X-ray structure of the Fe/S containing (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase (LytB) of the pathogenic protozoa Plasmodium falciparum which catalyzes the terminal step of the MEP pathway. The cloverleaf fold and the active site of P. falciparum LytB corresponds to those of the Aquifex aeolicus and Escherichia coli enzymes. Its distinct electron donor [2Fe-2S] ferredoxin was modeled to its binding site by docking calculations. The presented structural data provide a platform for a rational search of anti-malarian drugs.

Keywords: (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate; (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase; 2-C-methyl-d-erythritol-2,4-cyclo-diphosphate; 2-C-methyl-d-erythritol-4-phosphate; DMAPP; Drug design; HMBPP; IPP; Isoprenoid biosynthesis; LytB; MEP; MEcPP; Plasmodium falciparum; X-ray structure; dimethylallyl diphosphate; isopentenyl diphosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Escherichia coli / enzymology
  • Escherichia coli / metabolism
  • Ferredoxins / metabolism
  • Models, Molecular
  • Molecular Docking Simulation
  • Organophosphorus Compounds / metabolism*
  • Oxidoreductases / chemistry*
  • Oxidoreductases / metabolism*
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / metabolism


  • (E)-4-hydroxy-3-methylbut-2-enyl diphosphate
  • Ferredoxins
  • Organophosphorus Compounds
  • Protozoan Proteins
  • Oxidoreductases