The Structure-Function Relationship of Human Bleomycin Hydrolase: Mutation of a Cysteine Protease into a Serine Protease

Yi Zhen Zheng, Jingxuan Cui, Yung Lin Wang, Szu Jo Huang, En Chi Lin, Sheng Cih Huang, Jeffrey D. Rudolf, Xiaohui Yan, Chin Yuan Chang*

*此作品的通信作者

研究成果: Article同行評審

摘要

Human bleomycin hydrolase (hBH) catalyzes deamidation of the anticancer drug bleomycins (BLM). This enzyme is involved in BLM detoxification and drug resistance. Herein, we report the putative BLM-binding site and catalytic mechanism of hBH. The crystal structures and biochemical studies suggest that hBH cleaves its C-terminal residue without significant preference for the type of amino acid, and therefore can accordingly accommodate the β-aminoalanine amide moiety of BLM for deamidation. Interestingly, hBH is capable of switching from a cysteine protease to a serine protease that is unable to cleave the secondary amide of hBH C-terminus but reacts with the primary amide of BLMs.

原文English
文章編號e202200186
期刊ChemBioChem
23
發行號12
DOIs
出版狀態Published - 20 6月 2022

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