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Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila

DOI: 10.1038/s41467-020-18696-y DOI Help

Authors: Beatriz Trastoy (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Andreas Naegeli (Genovis AB) , Itxaso Anso (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Jonathan Sjögren (Genovis AB) , Marcelo Guerin (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); IKERBASQUE, Basque Foundation for Science)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: September 2020
Diamond Proposal Number(s): 20113

Open Access Open Access

Abstract: Akkermansia muciniphila is a mucin-degrading bacterium commonly found in the human gut that promotes a beneficial effect on health, likely based on the regulation of mucus thickness and gut barrier integrity, but also on the modulation of the immune system. In this work, we focus in OgpA from A. muciniphila, an O-glycopeptidase that exclusively hydrolyzes the peptide bond N-terminal to serine or threonine residues substituted with an O-glycan. We determine the high-resolution X-ray crystal structures of the unliganded form of OgpA, the complex with the glycodrosocin O-glycopeptide substrate and its product, providing a comprehensive set of snapshots of the enzyme along the catalytic cycle. In combination with O-glycopeptide chemistry, enzyme kinetics, and computational methods we unveil the molecular mechanism of O-glycan recognition and specificity for OgpA. The data also contribute to understanding how A. muciniphila processes mucins in the gut, as well as analysis of post-translational O-glycosylation events in proteins.

Journal Keywords: Glycobiology; Microbiome; Proteases; X-ray crystallography

Diamond Keywords: Gut Microbiota; Enzymes; Bacteria

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: BL13-XALOC at ALBA

Added On: 30/09/2020 09:08

Discipline Tags:

Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)