Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum at 2.25 A resolution reveals intriguing extra electron density in the active site

Proteins. 2006 Mar 15;62(3):570-7. doi: 10.1002/prot.20801.


The crystal structure of D-glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH) from the major malaria parasite Plasmodium falciparum is solved at 2.25 A resolution. The structure of PfGAPDH is of interest due to the dependence of the malaria parasite in infected human erythrocytes on the glycolytic pathway for its energy generation. Recent evidence suggests that PfGAPDH may also be required for other critical activities such as apical complex formation. The cofactor NAD(+) is bound to all four subunits of the tetrameric enzyme displaying excellent electron densities. In addition, in all four subunits a completely unexpected large island of extra electron density in the active site is observed, approaching closely the nicotinamide ribose of the NAD(+). This density is most likely the protease inhibitor AEBSF, found in maps from two different crystals. This putative AEBSF molecule is positioned in a crucial location and hence our structure, with expected and unexpected ligands bound, can be of assistance in lead development and design of novel antimalarials.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cytoplasm / enzymology
  • Glyceraldehyde-3-Phosphate Dehydrogenases / chemistry*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / chemistry
  • NAD / metabolism
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / genetics
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Recombinant Proteins / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Static Electricity


  • Protein Subunits
  • Protozoan Proteins
  • Recombinant Proteins
  • NAD
  • Glyceraldehyde-3-Phosphate Dehydrogenases

Associated data

  • PDB/2B4R
  • PDB/2B4T