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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fabd1f28b66b4a33a5fbc85e3dd477c6
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spelling	oai:doaj.org-article:fabd1f28b66b4a33a5fbc85e3dd477c62021-12-02T16:06:31ZX-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid10.1038/s41598-017-05627-z2045-2322https://doaj.org/article/fabd1f28b66b4a33a5fbc85e3dd477c62017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05627-zhttps://doaj.org/toc/2045-2322Abstract 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.Christian LizakLiam J. WorrallLars BaumannMoritz M. PfleidererGesa VolkersTianjun SunLyann SimWarren WakarchukStephen G. WithersNatalie C. J. StrynadkaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	x-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fabd1f28b66b4a33a5fbc85e3dd477c6
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X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid

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