8X6Y

Crystal structure of EfCDA

Summary for 8X6Y

• Entry DOI: 10.2210/pdb8x6y/pdb
• Related: 8X6U
• Descriptor: EfCDA, CACODYLATE ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: cytidine deaminase, hydrolase
• Biological source: Enterococcus
• Total number of polymer chains: 2
• Total formula weight: 29381.64

Authors

Jiang, L.,Huang, Y. (deposition date: 2023-11-22, release date: 2024-11-27, Last modification date: 2025-06-11)

Primary citation

Jiang, L.,Zhang, L.,Shu, Y.,Zhang, Y.,Gao, L.,Qiu, S.,Zhang, W.,Dai, W.,Chen, S.,Huang, Y.,Liu, Y.
Deciphering the role of Enterococcus faecium cytidine deaminase in gemcitabine resistance of gallbladder cancer.
J.Biol.Chem., 300:107171-107171, 2024

PubMed Abstract: Gemcitabine-based chemotherapy is a cornerstone of standard care for gallbladder cancer (GBC) treatment. Still, drug resistance remains a significant challenge, influenced by factors such as tumor-associated microbiota impacting drug concentrations within tumors. Enterococcus faecium, a member of tumor-associated microbiota, was notably enriched in the GBC patient cluster. In this study, we investigated the biochemical characteristics, catalytic activity, and kinetics of the cytidine deaminase of E. faecium (EfCDA). EfCDA showed the ability to convert gemcitabine to its metabolite 2',2'-difluorodeoxyuridine. Both EfCDA and E. faecium can induce gemcitabine resistance in GBC cells. Moreover, we determined the crystal structure of EfCDA, in its apo form and in complex with 2', 2'-difluorodeoxyuridine at high resolution. Mutation of key residues abolished the catalytic activity of EfCDA and reduced the gemcitabine resistance in GBC cells. Our findings provide structural insights into the molecular basis for recognizing gemcitabine metabolite by a bacteria CDA protein and may provide potential strategies to combat cancer drug resistance and improve the efficacy of gemcitabine-based chemotherapy in GBC treatment.

PubMed: 38492776
DOI: 10.1016/j.jbc.2024.107171

Experimental method

X-RAY DIFFRACTION (1.56 Å)