7ZOB

Metagenomic cytidine deaminase Cdd

Summary for 7ZOB

• Entry DOI: 10.2210/pdb7zob/pdb
• Descriptor: Metagenomic cytidine deaminase Cdd, ZINC ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (5 entities in total)
• Functional Keywords: hydrolase
• Biological source: uncultured bacterium
• Total number of polymer chains: 8
• Total formula weight: 125671.73

Authors

Tamulaitiene, G.,Urbeliene, N.,Meskys, R. (deposition date: 2022-04-25, release date: 2023-02-01, Last modification date: 2024-02-07)

Primary citation

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.
Cytidine deaminases catalyze the conversion of N ( S , O ) 4 -substituted pyrimidine nucleosides.
Sci Adv, 9:eade4361-eade4361, 2023

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 -acyl-cytidines, -alkyl-cytidines, and -alkyloxycarbonyl-cytidines, and -alkylthio-uridines and -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.

PubMed: 36735785
DOI: 10.1126/sciadv.ade4361

Experimental method

X-RAY DIFFRACTION (1.2 Å)