7OQD

A single sulfatase is required for metabolism of colonic mucin O-glycans and intestinal colonization by a symbiotic human gut bacterium (BT1636-S1_20)

This is a non-PDB format compatible entry.

Summary for 7OQD

• Entry DOI: 10.2210/pdb7oqd/pdb
• Descriptor: Arylsulfatase, 3-O-sulfo-beta-D-galactopyranose, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: carbohydrate sulfatase, mucin, microbiome, bacteroides, hydrolase
• Biological source: Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482)
• Total number of polymer chains: 1
• Total formula weight: 58329.61

Authors

Sofia de Jesus Vaz Luis, A.,Basle, A.,Martens, E.C.,Cartmell, A. (deposition date: 2021-06-03, release date: 2021-10-27, Last modification date: 2024-01-31)

Primary citation

Luis, A.S.,Jin, C.,Pereira, G.V.,Glowacki, R.W.P.,Gugel, S.R.,Singh, S.,Byrne, D.P.,Pudlo, N.A.,London, J.A.,Basle, A.,Reihill, M.,Oscarson, S.,Eyers, P.A.,Czjzek, M.,Michel, G.,Barbeyron, T.,Yates, E.A.,Hansson, G.C.,Karlsson, N.G.,Cartmell, A.,Martens, E.C.
A single sulfatase is required to access colonic mucin by a gut bacterium.
Nature, 598:332-337, 2021

PubMed Abstract: Humans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a barrier that separates these microorganisms from the intestinal epithelium. Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate degradation of the complex O-glycans found in mucins. In the distal colon, these glycans are heavily sulfated, but specific sulfatases that are active on colonic mucins have not been identified. Here we show that sulfatases are essential to the utilization of distal colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron. We characterized the activity of 12 different sulfatases produced by this species, showing that they are collectively active on all known sulfate linkages in O-glycans. Crystal structures of three enzymes provide mechanistic insight into the molecular basis of substrate specificity. Unexpectedly, we found that a single sulfatase is essential for utilization of sulfated O-glycans in vitro and also has a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by a prominent group of gut bacteria, an important process for both normal microbial gut colonization and diseases such as inflammatory bowel disease.

PubMed: 34616040
DOI: 10.1038/s41586-021-03967-5

Experimental method

X-RAY DIFFRACTION (2.3 Å)