ORCID Profile
0000-0003-1346-6435
Current Organisation
University of Tokyo
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Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.CHEMBIOL.2017.03.012
Abstract: Breast-fed infants generally have a bifidobacteria-rich microbiota with recent studies indicating that human milk oligosaccharides (HMOs) selectively promote bifidobacterial growth. Bifidobacterium bifidum possesses a glycoside hydrolase family 20 lacto-N-biosidase for liberating lacto-N-biose I from lacto-N-tetraose, an abundant HMO unique to human milk, while Bifidobacterium longum subsp. longum has a non-classified enzyme (LnbX). Here, we determined the crystal structure of the catalytic domain of LnbX and provide evidence for creation of a novel glycoside hydrolase family, GH136. The structure, in combination with inhibition and mutation studies, provides insight into the molecular mechanism and broader substrate specificity of this enzyme. Moreover, through genetic studies, we show that lnbX is indispensable for B. longum growth on lacto-N-tetraose and is a key genetic factor for persistence in the gut of breast-fed infants. Overall, this study reveals possible evolutionary routes for the emergence of symbiosis between humans and bifidobacterial species in the infant gut.
Publisher: Elsevier BV
Date: 04-2013
Publisher: Elsevier BV
Date: 07-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5CC05494J
Abstract: Synthesis and structural analysis of rationally developed inhibitors.
Publisher: Springer Science and Business Media LLC
Date: 02-03-2023
Publisher: Cold Spring Harbor Laboratory
Date: 28-07-2023
DOI: 10.1101/2023.07.28.550916
Abstract: β- N -Acetylgalactosamine-containing glycans play essential roles in several biological processes, including cell adhesion, signal transduction, and immune responses. β- N -Acetylgalactosaminidases hydrolyze β- N -acetylgalactosamine linkages of various glycoconjugates. However, their biological significance remains ambiguous, primarily because only one type of enzyme, exo-β- N -acetylgalactosaminidases that specifically act on β- N -acetylgalactosamine residues, has been documented so far. In this study, we identified three novel glycoside hydrolase families distributed among all three domains of life and characterized eight novel β- N -acetylgalactosaminidases and β- N -acetylhexosaminidase through sequence-based screening of deep-sea metagenomes and subsequent searching of public protein databases. Despite low sequence similarity, the crystal structures of these enzymes demonstrate that all enzymes share a prototype structure and ersify their substrate specificities (endo-, dual-endo/exo-, and exo-) through the accumulation of mutations and insertional amino acid sequences. The erse β- N -acetylgalactosaminidases reported in this study could facilitate the comprehension of their structures and functions and present novel evolutionary pathways for expanding their substrate specificity.
No related grants have been discovered for Shinya Fushinobu.