1QXS

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

1QXS の概要

• エントリーDOI: 10.2210/pdb1qxs/pdb
• 関連するPDBエントリー: 1K3T 1ML3
• 分子名称: Glyceraldehyde 3-phosphate dehydrogenase, glycosomal, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 3-HYDROXY-2-OXO-4-PHOPHONOXY- BUTYL)-PHOSPHONIC ACID, ... (4 entities in total)
• 機能のキーワード: ggapdh 1, 3-bpga analogue complex, oxidoreductase
• 由来する生物種: Trypanosoma cruzi
• 細胞内の位置: Glycosome: P22513
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 159367.92

構造登録者

Castilho, M.S.,Pavao, F.,Oliva, G. (登録日: 2003-09-08, 公開日: 2004-05-11, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.75 Å)