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PXD031225-1

PXD031225 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructure-guided mutagenesis of a mucin-selective metalloprotease from Akkermansia muciniphila alters substrate preferences
DescriptionAkkermansia muciniphila, a mucin-degrading microbe found in the human gut, is often associated with positive health outcomes. The abundance of Akkermansia 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 Akkermansia 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 at 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. Mutagenesis of these residues resulted in altered substrate preferences down to the glycan level, providing insight into the structural determinants of O-glycan recognition.
HostingRepositoryPRIDE
AnnounceDate2022-08-28
AnnouncementXMLSubmission_2022-08-27_22:22:57.874.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNicholas Riley
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListcomplex glycosylation
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-25 00:49:49ID requested
12022-08-27 22:22:58announced
22023-11-14 08:55:07announced2023-11-14: Updated project metadata.
Publication List
10.1016/J.JBC.2022.101917;
Keyword List
submitter keyword: X-ray crystallography, enzyme structure, metalloprotease, O-glycosylation, mucin, mucinase, molecular docking, microbiome
Contact List
Carolyn Bertozzi
contact affiliationDepartment of Chemistry, Stanford ChEM-H
contact emailbertozzi@stanford.edu
lab head
Nicholas Riley
contact affiliationStanford University
contact emailriley.nicholasm@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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