7V5S

Crystal structure of human bleomycin hydrolase C73A mutant

7V5S の概要

• エントリーDOI: 10.2210/pdb7v5s/pdb
• 分子名称: Bleomycin hydrolase, TETRAETHYLENE GLYCOL, TRIETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: cysteine protease, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55111.79

構造登録者

Chang, C.Y.,Zheng, Y.Z.,Huang, S.J.,Wang, Y.L.,Toh, S.I.,Lin, E.C. (登録日: 2021-08-18, 公開日: 2022-06-29, 最終更新日: 2023-11-29)

主引用文献

Zheng, Y.Z.,Cui, J.,Wang, Y.L.,Huang, S.J.,Lin, E.C.,Huang, S.C.,Rudolf, J.D.,Yan, X.,Chang, C.Y.
The Structure-Function Relationship of Human Bleomycin Hydrolase: Mutation of a Cysteine Protease into a Serine Protease.
Chembiochem, 23:e202200186-e202200186, 2022

PubMed 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.

PubMed: 35467071
DOI: 10.1002/cbic.202200186

実験手法

X-RAY DIFFRACTION (3.02 Å)