6YRO

Streptococcus suis SadP mutant - N285D

Summary for 6YRO

• Entry DOI: 10.2210/pdb6yro/pdb
• Descriptor: SadP, GLYCEROL, SODIUM ION, ... (4 entities in total)
• Functional Keywords: bacterial adhesion, glycoconjugates, streptococcus suis, galabiose, adhesins, sugar binding protein
• Biological source: Streptococcus suis
• Total number of polymer chains: 5
• Total formula weight: 127483.43

Authors

Papageorgiou, A.C.,Haataja, S. (deposition date: 2020-04-20, release date: 2020-08-19, Last modification date: 2024-01-24)

Primary citation

Madar Johansson, M.,Belurier, E.,Papageorgiou, A.C.,Sundin, A.P.,Rahkila, J.,Kallonen, T.,Nilsson, U.J.,Maatsola, S.,Nyholm, T.K.M.,Kapyla, J.,Corander, J.,Leino, R.,Finne, J.,Teneberg, S.,Haataja, S.
The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease.
J.Biol.Chem., 295:14305-14324, 2020

PubMed Abstract: is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic are limited, new therapeutic approaches are needed. The virulence factor adhesin P (SadP) recognizes the galabiose Galα1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes P and P We show here that subtype P is distributed in the systemic strains causing meningitis, whereas type P is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype P strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type P SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type P SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type P SadP binding to Gb4 could be used to selectively target in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.

PubMed: 32796033
DOI: 10.1074/jbc.RA120.014818

Experimental method

X-RAY DIFFRACTION (2.05 Å)