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The distinct biochemical property enables thymidylate kinase as a drug target and participates in pyrimidine drug sensitivity in Candida albicans

biorxiv. 2018; 
Chang-Yu Huang, Yee-Chun Chen, Betty A. Wu-Hsieh, Jim-Min Fang, Zee-Fen Chang
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Codon Optimization C. albicans CDC8 in pUC57 was purchased from GenScript (#5001191-1). Due to the difference in CTG codon usage for serine in C. albicans and leucine in E. coli and S. cerevisiae, the expression of CDC8 gene in E. coli and S.  Get A Quote

摘要

The ability to overcome drug resistance in outbreaks of Candida albicans infection is an unmet need in health management. Here, we investigated CDC8, which encodes thymidylate kinase (TMPK), as a potential drug target for the treatment of C. albicansinfection. In this study, we found that the specific region spanning amino acids 106-123, namely, the Ca-loop of C. albicans TMPK (CaTMPK) contributes to the hyperactivity of this enzyme compared to the human enzyme (hTMPK) and to the utilization of deoxyuridine monophosphate (dUMP)/ deoxy-5-Fluorouridine monophosphate (5-FdUMP) as a substrate. Notably, CaTMPK but not hTMPK enables dUTP/5-FdUTP-mediated DNA toxicity in yeast. CRISPR-mediated deletion of this C... More

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