7SCI
AM0627 metallopeptidase from Akkermansia muciniphila
Summary for 7SCI
| Entry DOI | 10.2210/pdb7sci/pdb |
| Descriptor | Peptidase M60 domain-containing protein, ZINC ION, TRIETHYLENE GLYCOL, ... (6 entities in total) |
| Functional Keywords | metalloenzyme, o-glycoprotease, mucinase, hydrolase |
| Biological source | Akkermansia muciniphila (strain ATCC BAA-835 / DSM 22959 / JCM 33894 / BCRC 81048 / CCUG 64013 / CIP 107961 / Muc) |
| Total number of polymer chains | 1 |
| Total formula weight | 55930.88 |
| Authors | Fernandez, D.,Bertozzi, C.R.,Shon, D.J. (deposition date: 2021-09-28, release date: 2022-04-27, Last modification date: 2023-10-18) |
| Primary citation | Shon, D.J.,Fernandez, D.,Riley, N.M.,Ferracane, M.J.,Bertozzi, C.R. Structure-guided mutagenesis of a mucin-selective metalloprotease from Akkermansia muciniphila alters substrate preferences. J.Biol.Chem., 298:101917-101917, 2022 Cited by PubMed Abstract: Akkermansia muciniphila, a mucin-degrading microbe found in the human gut, is often associated with positive health outcomes. The abundance of A. muciniphila is modulated by the presence and accessibility of nutrients, which can be derived from diet or host glycoproteins. In particular, the ability to degrade host mucins, a class of proteins carrying densely O-glycosylated domains, provides a competitive advantage in the sustained colonization of niche mucosal environments. Although A. muciniphila is known to rely on mucins as a carbon and nitrogen source, the enzymatic machinery used by this microbe to process mucins in the gut is not yet fully characterized. Here, we focus on the mucin-selective metalloprotease, Amuc_0627 (AM0627), which is known to cleave between adjacent residues carrying truncated core 1 O-glycans. We showed that this enzyme is capable of degrading purified mucin 2 (MUC2), the major protein component of mucus in the gut. An X-ray crystal structure of AM0627 (1.9 Å resolution) revealed O-glycan-binding residues that are conserved between structurally characterized enzymes from the same family. We further rationalized the substrate cleavage motif using molecular modeling to identify nonconserved glycan-interacting residues. We conclude that mutagenesis of these residues resulted in altered substrate preferences down to the glycan level, providing insight into the structural determinants of O-glycan recognition. PubMed: 35405095DOI: 10.1016/j.jbc.2022.101917 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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