5g2t
BT1596 in complex with its substrate 4,5 unsaturated uronic acid alpha 1,4 D-Glucosamine-2-N, 6-O-disulfate
Structural highlights
FunctionHEXSF_BACTN Exosulfatase involved in the degradation of the glycosaminoglycans (GAGs) chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS). 2-O-sulfatase active on unsaturated non-reducing end hexuronate units. Has a slight preference for HS-derived structures (PubMed:25002587). GAG-specific sulfatases play a key role in the persistence of the major human gut symbiont B.thetaiotaomicron in the host gastrointestinal tract (PubMed:25002587).[1] [2] Publication Abstract from PubMedThe human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation. It is possible that the bacterium recruits lyases with highly plastic specificities and expresses a repertoire of enzymes that target substructures of the glycosaminoglycans with variable sulfation or that the glycans are desulfated before cleavage by the lyases. To distinguish between these mechanisms, the components of the B. thetaiotaomicron Hep/HS degrading apparatus were analyzed. The data showed that the bacterium expressed a single-surface endo-acting lyase that cleaved HS, reflecting its higher molecular weight compared with Hep. Both Hep and HS oligosaccharides imported into the periplasm were degraded by a repertoire of lyases, with each enzyme displaying specificity for substructures within these glycosaminoglycans that display a different degree of sulfation. Furthermore, the crystal structures of a key surface glycan binding protein, which is able to bind both Hep and HS, and periplasmic sulfatases reveal the major specificity determinants for these proteins. The locus described here is highly conserved within the human gut Bacteroides, indicating that the model developed is of generic relevance to this important microbial community. How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans.,Cartmell A, Lowe EC, Basle A, Firbank SJ, Ndeh DA, Murray H, Terrapon N, Lombard V, Henrissat B, Turnbull JE, Czjzek M, Gilbert HJ, Bolam DN Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7037-7042. doi:, 10.1073/pnas.1704367114. Epub 2017 Jun 19. PMID:28630303[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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