9BLP

T450S mutant of repeat domain 2 from Clostridium perfringens adhesin CPE0147 with intramolecular ester bond

Summary for 9BLP

• Entry DOI: 10.2210/pdb9blp/pdb
• Related: 4MKM 4NI6 9BLO
• Descriptor: Surface anchored protein, 1,2-ETHANEDIOL, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: repeat domain, adhesin, bacterial adhesion, ig-like domain, unknown function
• Biological source: Clostridium perfringens B str. ATCC 3626
• Total number of polymer chains: 1
• Total formula weight: 17128.78

Authors

Squire, C.J.,Yosaatmadja, Y. (deposition date: 2024-05-01, release date: 2025-05-07, Last modification date: 2025-11-19)

Primary citation

Yosaatmadja, Y.,Ung, V.,Liu, X.,Zhao, Y.,Wardega, J.K.,Shetty, A.,Schoensee, S.,Leung, I.K.H.,Keown, J.R.,Goldstone, D.C.,Baker, E.N.,Young, P.G.,Mercadante, D.,Squire, C.J.
Protease mimicry: Dissecting the ester bond crosslinking mechanics in bacterial adhesin proteins.
Protein Sci., 34:e70238-e70238, 2025

PubMed Abstract: The ester bond crosslink discovered within bacterial adhesin proteins offers a captivating insight into the convergent evolution of enzyme-like machinery. Crystal structures reveal a putative catalytic triad comprising an acid-base-nucleophile combination and an oxyanion-like site that suggests a serine protease-like mechanism drives the crosslinking process. We now provide confirmation of the mechanism, revealing functional catalytic dyads or triads, and the recapitulation of protease machinery from a Pseudomonas bacterium and a human cytomegalovirus related only by convergent evolution. Molecular dynamics simulations suggest how a conservative threonine-to-serine mutation of the nucleophile induces hydrolysis and eliminates the ester bond crosslink. Collectively, our structural, functional, and computational efforts detail the molecular intricacies of intramolecular ester bond formation and underscore the convergent evolutionary adaptations of bacteria in exploiting enzyme-like machinery to protect essential adhesin proteins from the mechanical, biological, and chemical hostilities of their replicative niche.

PubMed: 40713781
DOI: 10.1002/pro.70238

Experimental method

X-RAY DIFFRACTION (1.2 Å)