2B4T

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

Summary for 2B4T

• Entry DOI: 10.2210/pdb2b4t/pdb
• Related: 2B4R
• Descriptor: glyceraldehyde-3-phosphate dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 4-(2-AMINOETHYL)BENZENESULFONYL FLUORIDE, ... (4 entities in total)
• Functional Keywords: structural genomics, psi, protein structure initiative, gapdh, glyceraldehyde-3-phosphate dehydrogenase, structural genomics of pathogenic protozoa consortium, sgpp, oxidoreductase
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum)
• Total number of polymer chains: 4
• Total formula weight: 153840.47

Authors

Robien, M.A.,Bosch, J.,Hol, W.G.J.,Structural Genomics of Pathogenic Protozoa Consortium (SGPP) (deposition date: 2005-09-26, release date: 2005-10-04, Last modification date: 2023-08-23)

Primary citation

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, J.M.,Hodgson, K.O.,Soltis, M.,Zucker, F.,Verlinde, C.L.,Merritt, E.A.,Schoenfeld, L.W.,Hol, W.G.
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, 62:570-577, 2006

PubMed Abstract: 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.

PubMed: 16345073
DOI: 10.1002/prot.20801

Experimental method

X-RAY DIFFRACTION (2.5 Å)