7v5l
Crystal structure of human bleomycin hydrolaseCrystal structure of human bleomycin hydrolase
Structural highlights
Function[BLMH_HUMAN] The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity (By similarity). Publication Abstract from PubMedHuman 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 beta-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. The Structure-Function Relationship of Human Bleomycin Hydrolase: Mutation of a Cysteine Protease into a Serine Protease.,Zheng YZ, Cui J, Wang YL, Huang SJ, Lin EC, Huang SC, Rudolf JD, Yan X, Chang CY Chembiochem. 2022 Jun 20;23(12):e202200186. doi: 10.1002/cbic.202200186. Epub, 2022 May 5. PMID:35467071[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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