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Robien, M.A., Bosch, J., Buckner, F.S., Van Voorhis, W.C., Worthey, E.A., Myler, P., Mehlin, C., Boni, E.E., Kalyuzhniy, O., Anderson, L., Lauricella, A., Gulde, S., Luft, J.R., DeTitta, G., Caruthers, M.J., Hodgson, K.O., Soltis, M., Zucker, F., Verlinde, M.J., Merritt, A.E. and Schoenfeld, W.L. (2006) Crystal Structure of Glyceraldehyde-3-Phosphate Dehydrogenase from Plasmodium falciparum at 2.25 Å Resolution Reveals Intriguing Extra Electron Density in the Active Site. PROTEINS: Structure Function Bioinformatics, 62, 570-577.
https://doi.org/10.1002/prot.20801

has been cited by the following article:

• TITLE: Molecular Docking of Selective Binding Affinity of Sulfonamide Derivatives as Potential Antimalarial Agents Targeting the Glycolytic Enzymes: GAPDH, Aldolase and TPI

  AUTHORS: Neville Forlemu, Porshaye Watkins, Joseph Sloop

  KEYWORDS: Malaria, Glycolytic Enzymes, AutoDock4.2, Dissociation Constant, Triosephosphate Isomerase, Binding Affinity

  JOURNAL NAME: Open Journal of Biophysics, Vol.7 No.1, January 19, 2017

  ABSTRACT: The parasite Plasmodium falciparum is responsible for the major world scourge malaria, a disease that affects 3.3 billion people worldwide. The development of new drugs is critical because of the diminished effectiveness of current antimalarial agents mainly due to parasitic resistance, side effects and cost. Molecular docking was used to explore structural motifs responsible for the interactions between triose phosphate isomerase (TPI), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and aldolase (ALD) from human and Plasmodium cells with 8 novel sufonylamide derivatives. All the ligands modeled, interact with all three enzymes in the micromolar range. The top ligand (sulfaE) shows a 70-fold increase in selective binding to pfTPI compared to hTPI (dissociation constant-KI of 7.83 μM and 0.177 μM for hTPI and pfTPI respectively), on par with antimalarial drug chloroquine.ALD and GAPDH form complexes with similar binding sites, comprising amino acids of similar chemical properties and polarities. Human TPI and pfTPI bind sulfonamide derivatives using two distinct binding sites and residues. Key residues at the dimer interface of pfTPI (VAL44, SER45, TYR48, GLN64, ASN65, VAL78) form a tight pocket with favorable polar contacts. The affinity with TPI is the most specific, stable, and selective suggesting pfTPI is a candidate for development of antimalarial drugs.