8DB6
Adenosine/guanosine nucleoside hydrolase
Summary for 8DB6
| Entry DOI | 10.2210/pdb8db6/pdb |
| Descriptor | Inosine-uridine preferring nucleoside hydrolase family protein, GLYCEROL, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | nucleoside, hydrolase, adenosine, guanosine, parasitic, inhibitor |
| Biological source | Trichomonas vaginalis |
| Total number of polymer chains | 4 |
| Total formula weight | 134341.94 |
| Authors | Muellers, S.N.,Allen, K.N.,Stockman, B.J. (deposition date: 2022-06-14, release date: 2022-09-07, Last modification date: 2024-04-03) |
| Primary citation | Muellers, S.N.,Nyitray, M.M.,Reynarowych, N.,Saljanin, E.,Benzie, A.L.,Schoenfeld, A.R.,Stockman, B.J.,Allen, K.N. Structure-Guided Insight into the Specificity and Mechanism of a Parasitic Nucleoside Hydrolase. Biochemistry, 61:1853-1861, 2022 Cited by PubMed Abstract: is the causative parasitic protozoan of the disease trichomoniasis, the most prevalent, nonviral sexually transmitted disease in the world. is a parasite that scavenges nucleosides from the host organism via catalysis by nucleoside hydrolase (NH) enzymes to yield purine and pyrimidine bases. One of the four NH enzymes identified within the genome of displays unique specificity toward purine nucleosides, adenosine and guanosine, but not inosine, and atypically shares greater sequence similarity to the pyrimidine hydrolases. Bioinformatic analysis of this enzyme, adenosine/guanosine-preferring nucleoside ribohydrolase (AGNH), was incapable of identifying the residues responsible for this uncommon specificity, highlighting the need for structural information. Here, we report the X-ray crystal structures of , unliganded AGNH and three additional structures of the enzyme bound to fragment and small-molecule inhibitors. Taken together, these structures facilitated the identification of residue Asp231, which engages in substrate interactions in the absence of those residues that typically support the canonical purine-specific tryptophan-stacking specificity motif. An altered substrate-binding pose is mirrored by repositioning within the protein scaffold of the His80 general acid/base catalyst. The newly defined structure-determined sequence markers allowed the assignment of additional NH orthologs, which are proposed to exhibit the same specificity for adenosine and guanosine alone and further delineate specificity classes for these enzymes. PubMed: 35994320DOI: 10.1021/acs.biochem.2c00361 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.02 Å) |
Structure validation
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