Download MendeleyCytidine deaminases catalyze the conversion of N ( S , O ) 4 -substituted pyrimidine nucleosides.
Urbeliene, N., Tiskus, M., Tamulaitiene, G., Gasparaviciute, R., Lapinskaite, R., Jauniskis, V., Sudzius, J., Meskiene, R., Tauraite, D., Skrodenyte, E., Urbelis, G., Vaitekunas, J., Meskys, R.(2023) Sci Adv 9: eade4361-eade4361
- PubMed: 36735785
- DOI: https://doi.org/10.1126/sciadv.ade4361
- Primary Citation of Related Structures:
7ZOB - PubMed Abstract:
Cytidine deaminases (CDAs) catalyze the hydrolytic deamination of cytidine and 2'-deoxycytidine to uridine and 2'-deoxyuridine. Here, we report that prokaryotic homo-tetrameric CDAs catalyze the nucleophilic substitution at the fourth position of N 4 -acyl-cytidines, N 4 -alkyl-cytidines, and N 4 -alkyloxycarbonyl-cytidines, and S 4 -alkylthio-uridines and O 4 -alkyl-uridines, converting them to uridine and corresponding amide, amine, carbamate, thiol, or alcohol as leaving groups. The x-ray structure of a metagenomic CDA_F14 and the molecular modeling of the CDAs used in this study show a relationship between the bulkiness of a leaving group and the volume of the binding pocket, which is partly determined by the flexible β3α3 loop of CDAs. We propose that CDAs that are active toward a wide range of substrates participate in salvage and/or catabolism of variously modified pyrimidine nucleosides. This identified promiscuity of CDAs expands the knowledge about the cellular turnover of cytidine derivatives, including the pharmacokinetics of pyrimidine-based prodrugs.
Organizational Affiliation:
Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Saulėtekio av., 10257 Vilnius, Lithuania.
