9EKN

Thomasclavelia ramosa Immunoglobulin A Protease Middle (Protease) Domain with C-terminal Domain #1 (Metal Chelated and Zinc Supplemented)

Summary for 9EKN

• Entry DOI: 10.2210/pdb9ekn/pdb
• Related: 9EKK 9EKM
• Descriptor: IgA protease, ZINC ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: m64 protease, secreted protein, immune modulating, zinc metalloprotease, hydrolase
• Biological source: Thomasclavelia ramosa
• Total number of polymer chains: 1
• Total formula weight: 62790.34

Authors

Tran, N.,Frenette, A.,Holyoak, T. (deposition date: 2024-12-02, release date: 2025-09-03, Last modification date: 2025-09-10)

Primary citation

Tran, N.,Frenette, A.,Holyoak, T.
Structure of the Thomasclavelia ramosa immunoglobulin A protease reveals a modular and minimizable architecture distinct from other immunoglobulin A proteases.
Proc.Natl.Acad.Sci.USA, 122:e2503549122-e2503549122, 2025

PubMed Abstract: Immunoglobulin A proteases (IgAPs) are a diverse group of enzymes secreted from bacteria that inhabit human mucosal tissues. These enzymes have convergently evolved to cleave human immunoglobulin A as a means of modulating and evading host immunity. Only two of three known IgAP families have been biochemically characterized beyond their initial discovery. Here, we show using solution-scattering, steady-state kinetic, and crystallographic approaches that the protease from , representing the uncharacterized third family, has a truly modular and minimizable protein architecture. This analysis also revealed a unique metal-associated domain that likely functions as a molecular spacer and generated a working hypothesis detailing the structural mechanism behind the enzyme's high substrate specificity. Our work provides an in-depth biochemical account of this IgAP family, paving the way for advancing clinically relevant IgAP-related research and our understanding of IgAPs as a whole.

PubMed: 40854123
DOI: 10.1073/pnas.2503549122

Experimental method

X-RAY DIFFRACTION (1.78 Å)