4AK1

Structure of BT4661, a SusE-like surface located polysaccharide binding protein from the Bacteroides thetaiotaomicron heparin utilisation locus

Summary for 4AK1

• Entry DOI: 10.2210/pdb4ak1/pdb
• Related: 4AK2
• Descriptor: BT_4661, SODIUM ION (3 entities in total)
• Functional Keywords: heparin-binding protein, heparan sulphate
• Biological source: BACTEROIDES THETAIOTAOMICRON
• Total number of polymer chains: 1
• Total formula weight: 77786.05

Authors

Lowe, E.C.,Basle, A.,Czjzek, M.,Thomas, S.,Murray, H.,Firbank, S.J.,Bolam, D.N. (deposition date: 2012-02-21, release date: 2013-03-06, Last modification date: 2024-05-08)

Primary citation

Cartmell, A.,Lowe, E.C.,Basle, A.,Firbank, S.J.,Ndeh, D.A.,Murray, H.,Terrapon, N.,Lombard, V.,Henrissat, B.,Turnbull, J.E.,Czjzek, M.,Gilbert, H.J.,Bolam, D.N.
How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans.
Proc. Natl. Acad. Sci. U.S.A., 114:7037-7042, 2017

PubMed Abstract: The 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 , 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 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 , indicating that the model developed is of generic relevance to this important microbial community.

PubMed: 28630303
DOI: 10.1073/pnas.1704367114

Experimental method

X-RAY DIFFRACTION (1.95 Å)