X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid
Abstract Polysialic acid (polySia) is a homopolymeric saccharide that is associated with some neuroinvasive pathogens and is found on selective cell types in their eukaryotic host. The presence of a polySia capsule on these bacterial pathogens helps with resistance to phagocytosis, cationic microbia...
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| Format: | Article |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05627-z |
| _version_ | 1818421793089650688 |
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| author | Christian Lizak Liam J. Worrall Lars Baumann Moritz M. Pfleiderer Gesa Volkers Tianjun Sun Lyann Sim Warren Wakarchuk Stephen G. Withers Natalie C. J. Strynadka |
| author_facet | Christian Lizak Liam J. Worrall Lars Baumann Moritz M. Pfleiderer Gesa Volkers Tianjun Sun Lyann Sim Warren Wakarchuk Stephen G. Withers Natalie C. J. Strynadka |
| author_sort | Christian Lizak |
| collection | DOAJ |
| description | Abstract Polysialic acid (polySia) is a homopolymeric saccharide that is associated with some neuroinvasive pathogens and is found on selective cell types in their eukaryotic host. The presence of a polySia capsule on these bacterial pathogens helps with resistance to phagocytosis, cationic microbial peptides and bactericidal antibody production. The biosynthesis of bacterial polySia is catalysed by a single polysialyltransferase (PST) transferring sialic acid from a nucleotide-activated donor to a lipid-linked acceptor oligosaccharide. Here we present the X-ray structure of the bacterial PST from Mannheimia haemolytica serotype A2, thereby defining the architecture of this class of enzymes representing the GT38 family. The structure reveals a prominent electropositive groove between the two Rossmann-like domains forming the GT-B fold that is suitable for binding of polySia chain products. Complex structures of PST with a sugar donor analogue and an acceptor mimetic combined with kinetic studies of PST active site mutants provide insight into the principles of substrate binding and catalysis. Our results are the basis for a molecular understanding of polySia biosynthesis in bacteria and might assist the production of polysialylated therapeutic reagents and the development of novel antibiotics. |
| first_indexed | 2024-12-14T13:16:00Z |
| format | Article |
| id | doaj.art-fabd1f28b66b4a33a5fbc85e3dd477c6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:16:00Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fabd1f28b66b4a33a5fbc85e3dd477c62022-12-21T23:00:04ZengNature PortfolioScientific Reports2045-23222017-07-017111310.1038/s41598-017-05627-zX-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acidChristian Lizak0Liam J. Worrall1Lars Baumann2Moritz M. Pfleiderer3Gesa Volkers4Tianjun Sun5Lyann Sim6Warren Wakarchuk7Stephen G. Withers8Natalie C. J. Strynadka9Department of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Chemistry, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Chemistry and Biology, Ryerson UniversityDepartment of Chemistry and Biology, Ryerson UniversityDepartment of Chemistry, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaAbstract Polysialic acid (polySia) is a homopolymeric saccharide that is associated with some neuroinvasive pathogens and is found on selective cell types in their eukaryotic host. The presence of a polySia capsule on these bacterial pathogens helps with resistance to phagocytosis, cationic microbial peptides and bactericidal antibody production. The biosynthesis of bacterial polySia is catalysed by a single polysialyltransferase (PST) transferring sialic acid from a nucleotide-activated donor to a lipid-linked acceptor oligosaccharide. Here we present the X-ray structure of the bacterial PST from Mannheimia haemolytica serotype A2, thereby defining the architecture of this class of enzymes representing the GT38 family. The structure reveals a prominent electropositive groove between the two Rossmann-like domains forming the GT-B fold that is suitable for binding of polySia chain products. Complex structures of PST with a sugar donor analogue and an acceptor mimetic combined with kinetic studies of PST active site mutants provide insight into the principles of substrate binding and catalysis. Our results are the basis for a molecular understanding of polySia biosynthesis in bacteria and might assist the production of polysialylated therapeutic reagents and the development of novel antibiotics.https://doi.org/10.1038/s41598-017-05627-z |
| spellingShingle | Christian Lizak Liam J. Worrall Lars Baumann Moritz M. Pfleiderer Gesa Volkers Tianjun Sun Lyann Sim Warren Wakarchuk Stephen G. Withers Natalie C. J. Strynadka X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid Scientific Reports |
| title | X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid |
| title_full | X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid |
| title_fullStr | X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid |
| title_full_unstemmed | X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid |
| title_short | X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid |
| title_sort | x ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid |
| url | https://doi.org/10.1038/s41598-017-05627-z |
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