Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase: structure, catalytic mechanism and targeted inhibitor design.
FEBS Lett
; 424(3): 131-5, 1998 Mar 13.
Article
en En
| MEDLINE
| ID: mdl-9580189
ABSTRACT
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 A includes the bound cofactor NAD+ and 90 water molecules per monomer and resulted in an Rfactor of 20.1%, Rfree = 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.
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Banco de datos:
MEDLINE
Asunto principal:
Trypanosoma cruzi
/
Inhibidores Enzimáticos
/
Gliceraldehído-3-Fosfato Deshidrogenasas
Límite:
Animals
/
Humans
Idioma:
En
Año:
1998
Tipo del documento:
Article