FEBS Letters | |
Trypanosoma cruzi glycosomal glyceraldehyde‐3‐phosphate dehydrogenase: structure, catalytic mechanism and targeted inhibitor design | |
Garratt, R.C2  Souza, D.H.F2  Guimarães, B.G2  Hannaert, V1  Araújo, A.P.U2  Jesus, W.D.P2  Oliva, G2  Michels, P.A.M1  | |
[1] Research Unit for Tropical Diseases, Christian de Duve Institute of Cellular Pathology (ICP) and Catholic University of Louvain, Ave. Hippocrate 74, B-1200 Brussels, Belgium;Instituto de Fı́sica de São Carlos, USP, P.O. Box 369, 13560-970 São Carlos, SP, Brazil | |
关键词: Glyceraldehyde-3-phosphate dehydrogenase; Crystal structure; Catalytic mechanism; Conformational change; Trypanosoma cruzi; | |
DOI : 10.1016/S0014-5793(98)00154-9 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
The structure of the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from glycosomes of the parasite Trypanosoma cruzi, causative agent of Chagas' disease, is reported. The final model at 2.8 Å includes the bound cofactor NAD+ and 90 water molecules per monomer and resulted in an R factor of 20.1%, R free=22.3%, with good geometry indicators. The structure has no ions bound at the active site resulting in a large change in the side chain conformation of Arg249 which as a consequence forms a salt bridge to Asp210 in the present structure. We propose that this conformational change could be important for the reaction mechanism and possibly a common feature of many GAPDH structures. Comparison with the human enzyme indicates that interfering with this salt bridge could be a new approach to specific inhibitor design, as the equivalent to Asp210 is a leucine in the mammalian enzymes.
【 授权许可】
Unknown
【 预 览 】
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