1QXS

CRYSTAL STRUCTURE OF Trypanosoma cruzi GLYCERALDEHYDE-3- PHOSPHATE DEHYDROGENASE COMPLEXED WITH AN ANALOGUE OF 1,3- BisPHOSPHO-D-GLYCERIC ACID

Summary for 1QXS

• Entry DOI: 10.2210/pdb1qxs/pdb
• Related: 1K3T 1ML3
• Descriptor: Glyceraldehyde 3-phosphate dehydrogenase, glycosomal, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 3-HYDROXY-2-OXO-4-PHOPHONOXY- BUTYL)-PHOSPHONIC ACID, ... (4 entities in total)
• Functional Keywords: ggapdh 1, 3-bpga analogue complex, oxidoreductase
• Biological source: Trypanosoma cruzi
• Cellular location: Glycosome: P22513
• Total number of polymer chains: 4
• Total formula weight: 159367.92

Authors

Castilho, M.S.,Pavao, F.,Oliva, G. (deposition date: 2003-09-08, release date: 2004-05-11, Last modification date: 2024-02-14)

Primary citation

Ladame, S.,Castilho, M.S.,Silva, C.H.,Denier, C.,Hannaert, V.,Perie, J.,Oliva, G.,Willson, M.
Crystal structure of Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase complexed with an analogue of 1,3-bisphospho-d-glyceric acid.
Eur.J.Biochem., 270:4574-4586, 2003

PubMed Abstract: We report here the first crystal structure of a stable isosteric analogue of 1,3-bisphospho-d-glyceric acid (1,3-BPGA) bound to the catalytic domain of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) in which the two phosphoryl moieties interact with Arg249. This complex possibly illustrates a step of the catalytic process by which Arg249 may induce compression of the product formed, allowing its expulsion from the active site. Structural modifications were introduced into this isosteric analogue and the respective inhibitory effects of the resulting diphosphorylated compounds on T. cruzi and Trypanosoma brucei gGAPDHs were investigated by enzymatic inhibition studies, fluorescence spectroscopy, site-directed mutagenesis, and molecular modelling. Despite the high homology between the two trypanomastid gGAPDHs (> 95%), we have identified specific interactions that could be used to design selective irreversible inhibitors against T. cruzi gGAPDH.

PubMed: 14622286
DOI: 10.1046/j.1432-1033.2003.03857.x

Experimental method

X-RAY DIFFRACTION (2.75 Å)