6N9J
X-ray structure of a secreted C11 cysteine protease from Bacteroides thetaiotaomicron in complex with an irreversible peptide inhibitor
Summary for 6N9J
| Entry DOI | 10.2210/pdb6n9j/pdb |
| Descriptor | Clostripain-related protein, Covalently bound peptide inhibitor (3 entities in total) |
| Functional Keywords | c11 protease, secreted, covalent peptide inhibitor, microbiome, commensal, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482) More |
| Total number of polymer chains | 4 |
| Total formula weight | 85858.65 |
| Authors | Wolan, D.W.,Gonzalez-Paez, G.E.,Roncase, E.J. (deposition date: 2018-12-03, release date: 2019-12-11, Last modification date: 2023-11-15) |
| Primary citation | 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 Cited by 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: 30835452DOI: 10.1021/acs.biochem.9b00098 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.17 Å) |
Structure validation
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