6MZO

X-ray Structure of an Inactive Zymogen C11 Protease from Parabacteroides distasonis

6MZO の概要

• エントリーDOI: 10.2210/pdb6mzo/pdb
• 分子名称: Inactive Zymogen C11 Protease, GLYCEROL (3 entities in total)
• 機能のキーワード: zymogen c11 protease, hydrolase
• 由来する生物種: Parabacteroides distasonis (strain ATCC 8503 / DSM 20701 / CIP 104284 / JCM 5825 / NCTC 11152)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42231.22

構造登録者

Wolan, D.W.,Gonzalez-Paez, G.E.,Roncase, E.J. (登録日: 2018-11-05, 公開日: 2019-04-17, 最終更新日: 2023-10-11)

主引用文献

Gonzalez-Paez, G.E.,Roncase, E.J.,Wolan, D.W.
X-ray structure of an inactive zymogen clostripain-like protease from Parabacteroides distasonis.
Acta Crystallogr D Struct Biol, 75:325-332, 2019

PubMed Abstract: The clostripain-like (C11) family of cysteine proteases are ubiquitously produced by the vast majority of the bacterial strains that make up the human distal gut microbiome. Recent reports show that some C11 proteases promote host immune responses and bacterial pathogenesis, including the induction of neutrophil phagocytosis and the activation of bacterial pathogenic toxins, respectively. The crystal structure of distapain, the only C11 protease predicted within the genome of the commensal bacterium Parabacteroides distasonis, was determined in the inactive zymogen state to 1.65 Å resolution. This is the first C11 protease structure of a zymogen, and the structure helped to uncover key unique conformations among critical active-site residues that are likely to assist in preserving the inactive protease. His135, a member of the catalytic dyad, is repositioned approximately 5.5 Å from the orientation found in active C11 structures and forms a hydrogen bond to Asp180 and a π-stacking interaction with Trp133. The structure sheds light on the potential importance of Asp180 and Trp133, as these residues are highly conserved across C11 proteases. Structure elucidation of C11 proteases will ultimately help to identify new ways to chemically and/or biologically regulate this family of enzymes, which represent potential drug-discovery targets in microbiome-related gastrointestinal diseases.

PubMed: 30950403
DOI: 10.1107/S2059798319000809

実験手法

X-RAY DIFFRACTION (1.653 Å)