| Title: |
Trypanosoma cruzi glycosomal glyceraldehyde‐3‐phosphate dehydrogenase: structure, catalytic mechanism and targeted inhibitor design |
| Authors: |
Souza, D.H.F; Garratt, R.C; Araújo, A.P.U; Guimarães, B.G; Jesus, W.D.P; Michels, P.A.M; Hannaert, V; Oliva, G |
| Source: |
FEBS Letters ; volume 424, issue 3, page 131-135 ; ISSN 0014-5793 1873-3468 |
| Publisher Information: |
Wiley |
| Publication Year: |
1998 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
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 Arg 249 which as a consequence forms a salt bridge to Asp 210 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 Asp 210 is a leucine in the mammalian enzymes. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1016/s0014-5793(98)00154-9 |
| DOI: |
10.1016/S0014-5793%2898%2900154-9 |
| Availability: |
https://doi.org/10.1016/s0014-5793(98)00154-9; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2FS0014-5793%2898%2900154-9; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2FS0014-5793(98)00154-9; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/S0014-5793%2898%2900154-9 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.D7576F54 |
| Database: |
BASE |