Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum

Abstract Infant gut-associated bifidobacteria has a metabolic pathway that specifically utilizes lacto-N-biose I (Gal-β1,3-GlcNAc) and galacto-N-biose (Gal-β1,3-GalNAc) from human milk and mucin glycans. UDP-glucose 4-epimerase (GalE) from Bifidobacterium longum (bGalE) catalyzes epimerization react...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Young-Woo Nam, Mamoru Nishimoto, Takatoshi Arakawa, Motomitsu Kitaoka, Shinya Fushinobu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/491b1a53d2ed41d68796339b7640d559
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:491b1a53d2ed41d68796339b7640d559
record_format	dspace
spelling	oai:doaj.org-article:491b1a53d2ed41d68796339b7640d5592021-12-02T15:08:09ZStructural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum10.1038/s41598-019-47591-w2045-2322https://doaj.org/article/491b1a53d2ed41d68796339b7640d5592019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47591-whttps://doaj.org/toc/2045-2322Abstract Infant gut-associated bifidobacteria has a metabolic pathway that specifically utilizes lacto-N-biose I (Gal-β1,3-GlcNAc) and galacto-N-biose (Gal-β1,3-GalNAc) from human milk and mucin glycans. UDP-glucose 4-epimerase (GalE) from Bifidobacterium longum (bGalE) catalyzes epimerization reactions of UDP-Gal into UDP-Glc and UDP-GalNAc into UDP-GlcNAc with the same level of activity that is required to send galacto-hexoses into glycolysis. Here, we determined the crystal structures of bGalE in three ternary complex forms: NAD+/UDP, NAD+/UDP-GlcNAc, and NAD+/UDP-Glc. The broad specificity of bGalE was explained by structural features of the binding pocket for the N-acetyl or C2 hydroxy group of the substrate. Asn200 is located in a pocket of the C2 group, and its side chain adopts different conformations in the complex structures with UDP-Glc and UDP-GlcNAc. On the other side, Cys299 forms a large pocket for the C5 sugar ring atom. The flexible C2 pocket and the large C5 pocket of bGalE are suitable for accommodating both the hydroxy and N-acetyl groups of the substrate during sugar ring rotation in the catalytic cycle. The substrate specificity and active site structure of bGalE were distinct from those of Esherichia coli GalE but similar to those of human GalE.Young-Woo NamMamoru NishimotoTakatoshi ArakawaMotomitsu KitaokaShinya FushinobuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Young-Woo Nam Mamoru Nishimoto Takatoshi Arakawa Motomitsu Kitaoka Shinya Fushinobu Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum
description	Abstract Infant gut-associated bifidobacteria has a metabolic pathway that specifically utilizes lacto-N-biose I (Gal-β1,3-GlcNAc) and galacto-N-biose (Gal-β1,3-GalNAc) from human milk and mucin glycans. UDP-glucose 4-epimerase (GalE) from Bifidobacterium longum (bGalE) catalyzes epimerization reactions of UDP-Gal into UDP-Glc and UDP-GalNAc into UDP-GlcNAc with the same level of activity that is required to send galacto-hexoses into glycolysis. Here, we determined the crystal structures of bGalE in three ternary complex forms: NAD+/UDP, NAD+/UDP-GlcNAc, and NAD+/UDP-Glc. The broad specificity of bGalE was explained by structural features of the binding pocket for the N-acetyl or C2 hydroxy group of the substrate. Asn200 is located in a pocket of the C2 group, and its side chain adopts different conformations in the complex structures with UDP-Glc and UDP-GlcNAc. On the other side, Cys299 forms a large pocket for the C5 sugar ring atom. The flexible C2 pocket and the large C5 pocket of bGalE are suitable for accommodating both the hydroxy and N-acetyl groups of the substrate during sugar ring rotation in the catalytic cycle. The substrate specificity and active site structure of bGalE were distinct from those of Esherichia coli GalE but similar to those of human GalE.
format	article
author	Young-Woo Nam Mamoru Nishimoto Takatoshi Arakawa Motomitsu Kitaoka Shinya Fushinobu
author_facet	Young-Woo Nam Mamoru Nishimoto Takatoshi Arakawa Motomitsu Kitaoka Shinya Fushinobu
author_sort	Young-Woo Nam
title	Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum
title_short	Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum
title_full	Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum
title_fullStr	Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum
title_full_unstemmed	Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum
title_sort	structural basis for broad substrate specificity of udp-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of bifidobacterium longum
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/491b1a53d2ed41d68796339b7640d559
work_keys_str_mv	AT youngwoonam structuralbasisforbroadsubstratespecificityofudpglucose4epimeraseinthehumanmilkoligosaccharidecatabolicpathwayofbifidobacteriumlongum AT mamorunishimoto structuralbasisforbroadsubstratespecificityofudpglucose4epimeraseinthehumanmilkoligosaccharidecatabolicpathwayofbifidobacteriumlongum AT takatoshiarakawa structuralbasisforbroadsubstratespecificityofudpglucose4epimeraseinthehumanmilkoligosaccharidecatabolicpathwayofbifidobacteriumlongum AT motomitsukitaoka structuralbasisforbroadsubstratespecificityofudpglucose4epimeraseinthehumanmilkoligosaccharidecatabolicpathwayofbifidobacteriumlongum AT shinyafushinobu structuralbasisforbroadsubstratespecificityofudpglucose4epimeraseinthehumanmilkoligosaccharidecatabolicpathwayofbifidobacteriumlongum
_version_	1718388249116803072

Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum

Ejemplares similares