Abstract
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.
Original language | English |
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Article number | e202200186 |
Journal | ChemBioChem |
Volume | 23 |
Issue number | 12 |
DOIs | |
State | Published - 20 Jun 2022 |
Keywords
- bleomycin
- crystal structures
- cysteine proteases
- hBH
- serine proteases