8RIH
Crystal structure of the Saccharomyces cerevisiae URH1p riboside hydrolase
Summary for 8RIH
| Entry DOI | 10.2210/pdb8rih/pdb |
| Descriptor | Uridine ribohydrolase, CALCIUM ION, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total) |
| Functional Keywords | nucleosidase, nucleoside hydrolase, riboside hydrolase, hydrolase |
| Biological source | Saccharomyces cerevisiae (brewer's yeast) |
| Total number of polymer chains | 2 |
| Total formula weight | 76835.32 |
| Authors | Degano, M.,Carriles, A.A. (deposition date: 2023-12-18, release date: 2024-07-03, Last modification date: 2024-10-09) |
| Primary citation | Carriles, A.A.,Muzzolini, L.,Minici, C.,Tornaghi, P.,Patrone, M.,Degano, M. Structure-Function Insights into the Dual Role in Nucleobase and Nicotinamide Metabolism and a Possible Use in Cancer Gene Therapy of the URH1p Riboside Hydrolase. Int J Mol Sci, 25:-, 2024 Cited by PubMed Abstract: The URH1p enzyme from the yeast has gained significant interest due to its role in nitrogenous base metabolism, particularly involving uracil and nicotinamide salvage. Indeed, URH1p was initially classified as a nucleoside hydrolase (NH) with a pronounced preference for uridine substrate but was later shown to also participate in a Preiss-Handler-dependent pathway for recycling of both endogenous and exogenous nicotinamide riboside (NR) towards NAD+ synthesis. Here, we present the detailed enzymatic and structural characterisation of the yeast URH1p enzyme, a member of the group I NH family of enzymes. We show that the URH1p has similar catalytic efficiencies for hydrolysis of NR and uridine, advocating a dual role of the enzyme in both NAD synthesis and nucleobase salvage. We demonstrate that URH1p has a monomeric structure that is unprecedented for members of the NH homology group I, showing that oligomerisation is not strictly required for the N-ribosidic activity in this family of enzymes. The size, thermal stability and activity of URH1p towards the synthetic substrate 5-fluoruridine, a riboside precursor of the antitumoral drug 5-fluorouracil, make the enzyme an attractive tool to be employed in gene-directed enzyme-prodrug activation therapy against solid tumours. PubMed: 39000137DOI: 10.3390/ijms25137032 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.74 Å) |
Structure validation
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