6N9J

X-ray structure of a secreted C11 cysteine protease from Bacteroides thetaiotaomicron in complex with an irreversible peptide inhibitor

6N9J の概要

• エントリーDOI: 10.2210/pdb6n9j/pdb
• 分子名称: Clostripain-related protein, Covalently bound peptide inhibitor (3 entities in total)
• 機能のキーワード: c11 protease, secreted, covalent peptide inhibitor, microbiome, commensal, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 85858.65

構造登録者

Wolan, D.W.,Gonzalez-Paez, G.E.,Roncase, E.J. (登録日: 2018-12-03, 公開日: 2019-12-11, 最終更新日: 2023-11-15)

主引用文献

Roncase, E.J.,Gonzalez-Paez, G.E.,Wolan, D.W.
X-ray Structures of Two Bacteroides thetaiotaomicron C11 Proteases in Complex with Peptide-Based Inhibitors.
Biochemistry, 58:1728-1737, 2019

PubMed Abstract: Commensal bacteria secrete proteins and metabolites to influence host intestinal homeostasis, and proteases represent a significant constituent of the components at the host:microbiome interface. Here, we determined the structures of the two secreted C11 cysteine proteases encoded by the established gut commensal Bacteroides thetaiotaomicron. We employed mutational analysis to demonstrate the two proteases, termed "thetapain" and "iotapain", undergo in trans autoactivation after lysine and/or arginine residues, as observed for other C11 proteases. We determined the structures of the active forms of thetapain and iotapain in complex with irreversible peptide inhibitors, Ac-VLTK-AOMK and biotin-VLTK-AOMK, respectively. Structural comparisons revealed key active-site interactions important for peptide recognition are more extensive for thetapain; however, both proteases employ a glutamate residue to preferentially bind small polar residues at the P2 position. Our results will aid in the design of protease-specific probes to ultimately understand the biological role of C11 proteases in bacterial fitness, elucidate their host and/or microbial substrates, and interrogate their involvement in microbiome-related diseases.

PubMed: 30835452
DOI: 10.1021/acs.biochem.9b00098

実験手法

X-RAY DIFFRACTION (2.17 Å)