3FZ0
Inosine-Guanosine Nucleoside Hydrolase (IG-NH)
Summary for 3FZ0
| Entry DOI | 10.2210/pdb3fz0/pdb |
| Related | 1KIC 1Q8F 2MAS 3B9X |
| Descriptor | Nucleoside hydrolase, putative, CALCIUM ION, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total) |
| Functional Keywords | nh fold, open alpha/beta structure, glycosidase, hydrolase |
| Biological source | Trypanosoma brucei |
| Total number of polymer chains | 4 |
| Total formula weight | 159736.57 |
| Authors | Vandemeulebroucke, A.,Minici, C.,Bruno, I.,Muzzolini, L.,Tornaghi, P.,Parkin, D.W.,Schramm, V.L.,Versees, W.,Steyaert, J.,Degano, M. (deposition date: 2009-01-23, release date: 2010-01-26, Last modification date: 2023-11-01) |
| Primary citation | Vandemeulebroucke, A.,Minici, C.,Bruno, I.,Muzzolini, L.,Tornaghi, P.,Parkin, D.W.,Versees, W.,Steyaert, J.,Degano, M. Structure and mechanism of the 6-oxopurine nucleosidase from Trypanosoma brucei brucei Biochemistry, 49:8999-9010, 2010 Cited by PubMed Abstract: Trypanosomes are purine-auxotrophic parasites that depend upon nucleoside hydrolase (NH) activity to salvage nitrogenous bases necessary for nucleic acid and cofactor synthesis. Nonspecific and purine-specific NHs have been widely studied, yet little is known about the 6-oxopurine-specific isozymes, although they are thought to play a primary role in the catabolism of exogenously derived nucleosides. Here, we report the first functional and structural characterization of the inosine-guanosine-specific NH from Trypanosoma brucei brucei. The enzyme shows near diffusion-limited efficiency coupled with a clear specificity for 6-oxopurine nucleosides achieved through a catalytic selection of these substrates. Pre-steady-state kinetic analysis reveals ordered product release, and a rate-limiting structural rearrangement that is associated with the release of the product, ribose. The crystal structure of this trypanosomal NH determined to 2.5 Å resolution reveals distinctive features compared to those of both purine- and pyrimidine-specific isozymes in the framework of the conserved and versatile NH fold. Nanomolar iminoribitol-based inhibitors identified in this study represent important lead compounds for the development of novel therapeutic strategies against trypanosomal diseases. PubMed: 20825170DOI: 10.1021/bi100697d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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