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
Date
12/14/2005Pubmed ID
16345073DOI
10.1002/prot.20801Scopus ID
2-s2.0-31944445647 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
Author List
Robien MA, Bosch J, Buckner FS, Van Voorhis WC, Worthey EA, Myler P, Mehlin C, Boni EE, Kalyuzhniy O, Anderson L, Lauricella A, Gulde S, Luft JR, DeTitta G, Caruthers JM, Hodgson KO, Soltis M, Zucker F, Verlinde CL, Merritt EA, Schoenfeld LW, Hol WGMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Conserved Sequence
Crystallography, X-Ray
Cytoplasm
Glyceraldehyde-3-Phosphate Dehydrogenases
Humans
Hydrogen Bonding
Models, Molecular
Molecular Sequence Data
NAD
Plasmodium falciparum
Protein Structure, Secondary
Protein Subunits
Protozoan Proteins
Recombinant Proteins
Sequence Alignment
Sequence Homology, Amino Acid
Static Electricity
