2XS3

Structure of karilysin catalytic MMP domain

Summary for 2XS3

• Entry DOI: 10.2210/pdb2xs3/pdb
• Related: 2XS4
• Descriptor: KARILYSIN PROTEASE, PEPTIDE ALA-PHE-THR-SER, ZINC ION, ... (5 entities in total)
• Functional Keywords: hydrolase, bacterial mmp, virulence factor, metalloprotease, zinc-dependent, peptidase
• Biological source: TANNERELLA FORSYTHIA; More
• Total number of polymer chains: 4
• Total formula weight: 38639.90

Authors

Cerda-Costa, N.,Guevara, T.,Karim, A.Y.,Ksiazek, M.,Nguyen, K.-A.,Arolas, J.L.,Potempa, J.,Gomis-Ruth, F.X. (deposition date: 2010-09-24, release date: 2010-11-03, Last modification date: 2023-12-20)

Primary citation

Cerda-Costa, N.,Guevara, T.,Karim, A.Y.,Ksiazek, M.,Nguyen, K.A.,Arolas, J.L.,Potempa, J.,Gomis-Ruth, F.X.
The Structure of the Catalytic Domain of Tannerella Forsythia Karilysin Reveals It is a Bacterial Xenologue of Animal Matrix Metalloproteinases.
Mol.Microbiol., 79:119-, 2011

PubMed Abstract: Metallopeptidases (MPs) are among virulence factors secreted by pathogenic bacteria at the site of infection. One such pathogen is Tannerella forsythia, a member of the microbial consortium that causes peridontitis, arguably the most prevalent infective chronic inflammatory disease known to mankind. The only reported MP secreted by T. forsythia is karilysin, a 52 kDa multidomain protein comprising a central 18 kDa catalytic domain (CD), termed Kly18, flanked by domains unrelated to any known protein. We analysed the 3D structure of Kly18 in the absence and presence of Mg(2+) or Ca(2+) , which are required for function and stability, and found that it evidences most of the structural features characteristic of the CDs of mammalian matrix metalloproteinases (MMPs). Unexpectedly, a peptide was bound to the active-site cleft of Kly18 mimicking a left-behind cleavage product, which revealed that the specificity pocket accommodates bulky hydrophobic side-chains of substrates as in mammalian MMPs. In addition, Kly18 displayed a unique Mg(2+) or Ca(2+) binding site and two flexible segments that could play a role in substrate binding. Phylogenetic and sequence similarity studies revealed that Kly18 is evolutionarily much closer to winged-insect and mammalian MMPs than to potential bacterial counterparts found by genomic sequencing projects. Therefore, we conclude that this first structurally characterized non-mammalian MMP is a xenologue co-opted through horizontal gene transfer during the intimate coexistence between T. forsythia and humans or other animals, in a very rare case of gene shuffling from eukaryotes to prokaryotes. Subsequently, this protein would have evolved in a bacterial environment to give rise to full-length karilysin that is furnished with unique flanking domains that do not conform to the general multidomain architecture of animal MMPs.

PubMed: 21166898
DOI: 10.1111/J.1365-2958.2010.07434.X

Experimental method

X-RAY DIFFRACTION (2.4 Å)