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| Open AccessDiatom fucan polysaccharide precipitates carbon during algal blooms
The fate of ocean carbon is determined by the balance between primary productivity and heterotrophic breakdown of that photosynthate. Here the authors show that diatoms produce a polysaccharide that resists bacterial degradation, accumulates, aggregates and stores carbon during spring blooms.
- Silvia Vidal-Melgosa
- , Andreas Sichert
- & Jan-Hendrik Hehemann
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Article
| Open AccessStructure of a full-length bacterial polysaccharide co-polymerase
Lipopolysaccharides, important components of the bacterial cell envelope, are synthesized at the inner membrane by the Wzx/Wzy-dependent assembly pathway. A cryo-EM structure of an intact E. coli WzzB, the polysaccharide co-polymerase component of this pathway, reveals details of the transmembrane, cytoplasmic domains and a conserved a proline-rich segment proximal to the C-terminal transmembrane helix.
- Benjamin Wiseman
- , Ram Gopal Nitharwal
- & Martin Högbom
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Article
| Open AccessReverse C-glycosidase reaction provides C-nucleotide building blocks of xenobiotic nucleic acids
C-nucleosides are analogues of the canonical N-nucleosides and, despite their synthetic value, biocatalysis has not targeted them yet. Here, the authors report a pseudouridine monophosphate C-glycosidase enzyme for selective 5-β-C-glycosylation of uracil and its derivatives from pentose 5- phosphate substrates.
- Martin Pfeiffer
- & Bernd Nidetzky
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| Open AccessStructure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation
AlfC transfucosidase is used to modulate fucosylation of glycans decorating monoclonal antibodies. Herein, structural and biophysical characterization reveals the enzymatic mechanism of AlfC and a blueprint for the design of AlfC mutants with novel specificities and functions.
- Erik H. Klontz
- , Chao Li
- & Eric J. Sundberg
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Article
| Open AccessAnalysis of inositol phosphate metabolism by capillary electrophoresis electrospray ionization mass spectrometry
Myo-Inositol phosphates (InsPs) and pyrophosphates (PP-InsPs) are important second messengers but their analysis remains challenging. Here, the authors develop a capillary electrophoresis-mass spectrometry method for the identification and quantitation of InsP and PP-InsP isomers in cells and tissues.
- Danye Qiu
- , Miranda S. Wilson
- & Henning J. Jessen
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Article
| Open AccessAssembling custom side chains on proteoglycans to interrogate their function in living cells
Currently, it is not possible to generate proteoglycans displaying glycosaminoglycan chains with specific structures. Here the authors show that by using an aldehyde tag-based methodology it is possible to insert these specific chains onto proteoglycans expressed on the cell surface.
- Wenshuang Wang
- , Naihan Han
- & Fuchuan Li
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Article
| Open AccessExploring and applying the substrate promiscuity of a C-glycosyltransferase in the chemo-enzymatic synthesis of bioactive C-glycosides
C-glycosides are of pharmaceutical interest due to their stability against in vivo hydrolysis, however their enzymatic synthesis faces challenges. Here, the authors report a C-glycosyltransferase from Aloe barbadensis catalysing the C-glycosylation of drug-like acceptors to generate bioactive C-glycosides.
- Kebo Xie
- , Xiaolin Zhang
- & Jungui Dai
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Article
| Open AccessA versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands
Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a family of immunomodulatory receptors expressed on cells of the hematopoietic lineage. Here the authors demonstrate an approach for the identification of the glycan ligands of Siglecs, which is also applicable to other families of glycan-binding proteins.
- Emily Rodrigues
- , Jaesoo Jung
- & Matthew S. Macauley
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Article
| Open AccessStructural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A
Neisseria meningitidis capsular polysaccharide (CPS) is a major virulence factor and vaccine formulations against Neisseria meningitidis serogroup A (NmA) contain O-acetylated CPS. Here, the authors provide mechanistic insights into CPS O-acetylation in NmA by determining the crystal structure of the O-acetyltransferase CsaC and NMR measurements further reveal that the CsaC-mediated reaction is regioselective for O3 and that the O4 modification results from spontaneous O-acetyl migration.
- Timm Fiebig
- , Johannes T. Cramer
- & Martina Mühlenhoff
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Article
| Open AccessWood hemicelluloses exert distinct biomechanical contributions to cellulose fibrillar networks
Hemicelluloses are an essential constituent of plant cell walls, but the individual biomechanical roles remain elusive. Here the authors report on the interaction of wood hemicellulose with bacterial cellulose during deposition and explore the resultant fibrillar architecture and mechanical properties.
- Jennie Berglund
- , Deirdre Mikkelsen
- & Francisco Vilaplana
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Article
| Open AccessA stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A
The Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) is a component of commercial vaccines, but is unstable. Here, the authors generate glycomimetic oligomers that demonstrate higher stability than their natural counterparts and induce protective antibodies in mice.
- Jacopo Enotarpi
- , Marta Tontini
- & Roberto Adamo
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Article
| Open AccessChemical synthesis of glycans up to a 128-mer relevant to the O-antigen of Bacteroides vulgatus
Glycans are abundant biomolecules that mediate essential biological processes, but their chemical synthesis is challenging. Here, the authors report the synthesis of glycans up to a 128-mer, which represents the O-antigen of Bacteroides vulgatus lipopolysaccharide and one of the longest synthetic glycans to date.
- Qian Zhu
- , Zhengnan Shen
- & Biao Yu
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Article
| Open AccessA nonenzymatic method for cleaving polysaccharides to yield oligosaccharides for structural analysis
While mass spectrometry-based proteomics largely relies on digesting proteins into peptides, there is no equivalent strategy for polysaccharide analysis. Here, the authors develop a chemical approach to break down poly- into oligosaccharides and present a workflow to identify polysaccharides by oligosaccharide fingerprinting.
- Matthew J. Amicucci
- , Eshani Nandita
- & Carlito B. Lebrilla
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Article
| Open AccessStructural signatures in EPR3 define a unique class of plant carbohydrate receptors
Exopolysaccharides (EPS) are perceived by legumes and regulate symbiosis with rhizobia. Here the authors describe the structure of the Lotus EPS receptor, EPR3 and show that it has atypical βαββ and βαβ folds that represent a structural signature for a unique class of EPS receptors in the plant kingdom.
- Jaslyn E. M. M. Wong
- , Kira Gysel
- & Kasper R. Andersen
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Article
| Open AccessEliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum
Bioproduction of hyaluronan needs increases in yield and greater diversity of the molecular weights. Here, the author increases hyaluronan production and diversifies the molecular weights through engineering the hyaluronan biosynthesis pathway and disruption of Corynebacterium glutamicum encapsulation caused by secreted hyaluronan.
- Yang Wang
- , Litao Hu
- & Zhen Kang
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Article
| Open AccessTrefoil factors share a lectin activity that defines their role in mucus
Trefoil factors (TFFs) protect the mucosa and have various reported binding activities, but whether they share a common interaction mechanism has remained unclear. Here, the authors provide structural and biochemical evidence that all three human TFFs are divalent lectins that recognise the same disaccharide.
- Michael A. Järvå
- , James P. Lingford
- & Ethan D. Goddard-Borger
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Article
| Open AccessShotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides
Heparan sulfates (HS) contain functionally relevant structural motifs, but determining their monosaccharide sequence remains challenging. Here, the authors develop an ion mobility mass spectrometry-based method that allows unambiguous characterization of HS sequences and structure-activity relationships.
- Rebecca L. Miller
- , Scott E. Guimond
- & Kevin Pagel
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Article
| Open AccessImproved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor
The secretion of blood coagulation factor V and factor VIII (FV and FVIII) are driven by secretion factors ERGIC-53 and MCDF2. Here, the authors report a 10 amino acid motif from FVIII that can enhance secretion of another glycoprotein erythropoietin (EPO).
- Hirokazu Yagi
- , Maho Yagi-Utsumi
- & Koichi Kato
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Article
| Open AccessStructural basis for substrate specificity and catalysis of α1,6-fucosyltransferase
Core-fucosylation of the N-glycan core is an essential biological modification and the α1,6- fucosyltransferase FUT8 is the only enzyme in humans that catalyses this modification through the addition of an α-1,6-linked fucose to N-glycans. Here the authors provide insights into FUT8 substrate recognition by determining the 1.95 Å crystal structure of human FUT8 complexed with GDP and a biantennary complex N-glycan.
- Ana García-García
- , Laura Ceballos-Laita
- & Ramon Hurtado-Guerrero
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Article
| Open AccessAlterations in promoter interaction landscape and transcriptional network underlying metabolic adaptation to diet
Metabolic adaptation to different diets results in changes to gene expression. Here, the authors characterise the chromatin landscape and transcriptional network in mice on a diet of high saturated fat, compared to a diet high in carbohydrate, finding a dramatic reprogramming of the liver transcriptional network.
- Yufeng Qin
- , Sara A. Grimm
- & Paul A. Wade
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Article
| Open AccessMetabolism of multiple glycosaminoglycans by Bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus
Glycosaminoglycans (GAGs) are an important nutrient source for the gut microbiome. Here, the authors characterize the genetic loci that underpins glycosaminoglycan utilization in Bacteroides thetaiotaomicron; providing insights into the metabolism of GAGs by a predominant member of the gut microbiota.
- Didier Ndeh
- , Arnaud Baslé
- & Alan Cartmell
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Article
| Open AccessCrystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy
Fukutin-related protein (FKRP) catalyses the addition of ribitol-phosphate (RboP) to the O-mannosyl glycan of α-dystroglycan and mutations in FKRP cause dystroglycanopathy. Here the authors provide insights into its oligomerization and recognition of the substrates, CDP-Rbo and the RboP-(phospho-)core M3 glycan, by determining the crystal structures of human FKRP.
- Naoyuki Kuwabara
- , Rieko Imae
- & Ryuichi Kato
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Article
| Open AccessMolecular architecture of softwood revealed by solid-state NMR
Understanding the interactions between the constituents of the cell walls in wood is important for understanding the mechanical properties. Here, the authors report on a solid-state NMR study of never-dried softwood, noticing differences to previous reports and develop a model of softwood architecture.
- Oliver M. Terrett
- , Jan J. Lyczakowski
- & Paul Dupree
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Article
| Open AccessInverting family GH156 sialidases define an unusual catalytic motif for glycosidase action
Sialidases are glycoside hydrolases that cleave sialosides. Here the authors define the 3-D structure, alone and in complex with products and inhibitors, of the CAZy family GH156 sialidase, EnvSia156, showing it displays a catalytical (β/α) 8-barrel domain distinct from other sialidases and allowing description of its inverting catalytic mechanism.
- Pedro Bule
- , Léa Chuzel
- & Gideon J. Davies
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Article
| Open AccessThe hydrolase LpqI primes mycobacterial peptidoglycan recycling
Bacterial growth and division require remodelling of the cell wall, which generates free peptidoglycan fragments. Here, Moynihan et al. show that Mycobacterium tuberculosis can recycle components of their peptidoglycan, and characterise a crucial enzyme required for this process.
- Patrick J. Moynihan
- , Ian T. Cadby
- & Gurdyal S. Besra
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Article
| Open AccessHighly sensitive CE-ESI-MS analysis of N-glycans from complex biological samples
In-depth characterization of complex glycomes is complicated by the immense structural diversity of glycans. Here, the authors present a mass spectrometry-based strategy for untargeted, sensitive glycan profiling and identify 167 N-glycan compositions in total human plasma.
- Guinevere S. M. Lageveen-Kammeijer
- , Noortje de Haan
- & Manfred Wuhrer
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Article
| Open AccessBacteroidetes use thousands of enzyme combinations to break down glycans
Bacteroidetes genomes contain polysaccharide utilization loci (PULs), each of which encodes enzymes for the breakdown of one particular glycan. By analyzing the enzyme composition of 13,537 PULs, the authors suggest that the natural glycan diversity is orders of magnitude lower than previously proposed.
- Pascal Lapébie
- , Vincent Lombard
- & Bernard Henrissat
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Article
| Open AccessReconstitution of the lipid-linked oligosaccharide pathway for assembly of high-mannose N-glycans
Attachment of the oligosaccharide Man9GlcNAc2 is required for glycoprotein folding and secretion but synthesizing this compound for structural and functional studies has remained challenging. Here, the authors achieve efficient Man9GlcNAc2 synthesis by reconstituting its biosynthetic pathway in vitro.
- Sheng-Tao Li
- , Tian-Tian Lu
- & Xiao-Dong Gao
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Article
| Open AccessBacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification
Glycan molecules can be modified directly on the cell surface via chemoenzymatic approaches. Here, the authors employ a set of four bacterial glycosyltransferases to develop a live cell-based killing assay to probe host cell glycan-mediated influenza A virus infection.
- Senlian Hong
- , Yujie Shi
- & Peng Wu
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Article
| Open AccessReversible histone glycation is associated with disease-related changes in chromatin architecture
Proteins continuously undergo non-enzymatic modifications such as glycation, which accumulate under physiological conditions but can be enhanced in disease. Here the authors characterise histone glycation, provide evidence that it affects chromatin, particularly in breast cancer, and identify DJ-1 as a deglycase.
- Qingfei Zheng
- , Nathaniel D. Omans
- & Yael David
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| Open AccessThe human gut Firmicute Roseburia intestinalis is a primary degrader of dietary β-mannans
How dietary β-mannans are utilized by gut Gram-positive bacteria is unclear. Here, the authors uncover the enzymatic pathway for β-mannan metabolism in Roseburia intestinalis and show that these polysaccharides promote beneficial gut bacteria, highlighting a potential for β-mannan-based therapeutic interventions.
- Sabina Leanti La Rosa
- , Maria Louise Leth
- & Bjørge Westereng
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Article
| Open AccessCyanobacterial antimetabolite 7-deoxy-sedoheptulose blocks the shikimate pathway to inhibit the growth of prototrophic organisms
Mother Nature is a valuable resource for the discovery of drug and agricultural chemicals. Here, the authors show that 7-deoxy-sedoheptulose produced by a cyanobacterium is an antimicrobial and herbicidal compound that acts through inhibition of 3-dehydroquniate synthase in the shikimate pathway.
- Klaus Brilisauer
- , Johanna Rapp
- & Karl Forchhammer
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Article
| Open AccessCrystal structure of the plant symporter STP10 illuminates sugar uptake mechanism in monosaccharide transporter superfamily
Plants are dependent on controlled sugar uptake via Monosaccharide Transporters, such as STP10, for correct organ development, sugar accumulation in fruits and microbial defense. Here authors present the crystal structure of STP10 bound to glucose which sheds light on the fundamental principles of sugar transport in the plant-unique MST superfamily.
- Peter Aasted Paulsen
- , Tânia F. Custódio
- & Bjørn Panyella Pedersen
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Article
| Open AccessLignin-polysaccharide interactions in plant secondary cell walls revealed by solid-state NMR
The interactions of lignin with polysaccharides in plant secondary cell walls are not well understood. Here the authors employ solid-state NMR measurements to analyse intact stems of maize, Arabidopsis, switchgrass and rice and observe that lignin self-aggregates and forms highly hydrophobic microdomains that make extensive surface contacts to xylan.
- Xue Kang
- , Alex Kirui
- & Tuo Wang
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Article
| Open AccessHighly modified and immunoactive N-glycans of the canine heartworm
The glycome of parasites can have immunomodulatory properties or help to avoid immune surveillance, but details are unknown. Here, Martini et al. characterize the N-glycome of the canine heartworm, reveal an unprecedented complexity, particularly in anionic N-glycans, and determine recognition by components of the immune system.
- Francesca Martini
- , Barbara Eckmair
- & Katharina Paschinger
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Article
| Open AccessHierarchical and programmable one-pot synthesis of oligosaccharides
The software Optimer has aided the programmable one-pot oligosaccharide synthesis with a library of 50 Building BLocks (BBLs). Here, the authors expanded Optimer's validated and virtual libraries of BBLs and developed Auto-CHO, a software which allows the one-pot programmable synthesis of more complex glycans.
- Cheng-Wei Cheng
- , Yixuan Zhou
- & Chi-Huey Wong
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Article
| Open AccessHemocyanin facilitates lignocellulose digestion by wood-boring marine crustaceans
Marine woodborers can digest woody biomass without the help of gut microbiota but the mechanism has remained unclear. Here, the authors provide evidence that the woodborer’s respiratory protein hemocyanin plays a central role in wood digestion and may offer a route toward biorefining of woody plant biomass.
- Katrin Besser
- , Graham P. Malyon
- & Simon J. McQueen-Mason
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Article
| Open AccessSugar-based bactericides targeting phosphatidylethanolamine-enriched membranes
Bacillus anthracis causes the infectious disease anthrax. Here, the authors synthesized deoxy glycosides that are effective against B. anthracis and related bacteria and found that these amphiphilic compounds kill bacteria via an unusual mechanism of action.
- Catarina Dias
- , João P. Pais
- & Amélia P. Rauter
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Article
| Open AccessA Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates
Polyfluorinated hexopyranoses display unique physical, chemical and biological properties, however their stereoselective synthesis is highly challenging. Here, the authors report a synthetic approach based on the chemical manipulation of inexpensive levoglucosan to obtain heavily fluorinated monosaccharides stereoselectively.
- Vincent Denavit
- , Danny Lainé
- & Denis Giguère
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Article
| Open AccessRevealing the mechanism for covalent inhibition of glycoside hydrolases by carbasugars at an atomic level
Mechanism-based inhibitors of glycoside hydrolases are useful probes for basic research and represent potential drug candidates. Here, the authors present a series of mechanism-based covalent α-galactosidase inhibitors and elucidate the kinetic and structural basis of their inhibitory activity.
- Weiwu Ren
- , Robert Pengelly
- & Andrew J. Bennet
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Article
| Open AccessGlycan recognition in globally dominant human rotaviruses
Human rotaviruses (RV) bind to histo-blood group antigens (HBGA) for attachment, but how different viral genotypes interact with HBGA isn’t known. Here, Hu et al. report crystal structures of a prevalent and a neonate-specific RV in complex with HBGA and provide insights into glycan recognition and age-restricted tropism of RVs.
- Liya Hu
- , Banumathi Sankaran
- & B. V. Venkataram Prasad
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Article
| Open AccessEngineering enhanced cellobiohydrolase activity
Cellobiohydrolases (CBHs) are critical for natural and industrial biomass degradation but their structure–activity relationships are not fully understood. Here, the authors present the biochemical and structural characterization of two CBHs, identifying protein regions that confer enhanced CBH activity.
- Larry E. Taylor II
- , Brandon C. Knott
- & Gregg T. Beckham
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Article
| Open AccessMolecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont
Polysaccharides are the primary structural cell wall and energy storage molecules of seaweed. Here, the authors show how the geographically restricted dietary polysaccharide agarose is selectively utilized by the human intestinal bacterium Bacteroides uniformis, providing insight into how carbohydrate metabolism evolves within the human microbiome.
- Benjamin Pluvinage
- , Julie M. Grondin
- & D. Wade Abbott
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Article
| Open AccessCell-based glycan arrays for probing glycan–glycan binding protein interactions
Glycans, interaction platforms protruding from the surface of cells, are hard to study due to their diverse architecture. Here, the authors present a method to obtain cells carrying defined glycans, which can then be used to find proteins specifically recognizing these tags.
- Jennie Grace Briard
- , Hao Jiang
- & Peng Wu
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Article
| Open AccessAn ancient family of lytic polysaccharide monooxygenases with roles in arthropod development and biomass digestion
LPMOs catalyze the oxidative breakdown of polysaccharides, thereby facilitating biomass degradation. By analyzing the digestive proteome of firebrats, the authors here identify a yet uncharacterized LPMO family and provide phylogenetic, structural and biochemical insights into its origin and functions.
- Federico Sabbadin
- , Glyn R. Hemsworth
- & Simon J. McQueen-Mason
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Article
| Open AccessStructural basis of the molecular ruler mechanism of a bacterial glycosyltransferase
The glycosyltransferase PglH transfers three terminal N-acetylgalactosamine (GalNAc) residues to a carrier, which is a prerequisite for bacterial protein N-glycosylation. Here authors present the crystal structures of PglH in three distinct states and show that a ‘ruler helix’ facilitates membrane attachment and glycan counting.
- Ana S. Ramírez
- , Jérémy Boilevin
- & Kaspar P. Locher
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Article
| Open AccessStructural basis for chitin acquisition by marine Vibrio species
Chitin degrading bacteria are important for marine ecosystems. Here the authors structurally and functionally characterize the Vibrio harveyi outer membrane diffusion channel chitoporin and give mechanistic insights into chito-oligosaccharide uptake.
- Anuwat Aunkham
- , Michael Zahn
- & Bert van den Berg
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Article
| Open AccessReassessment of chitosanase substrate specificities and classification
Chitosanases are classified according to their specificity in cleaving bonds at GlcNAc residues but the current system may be too simplistic. Here, the authors use quantitative mass spectrometry to revisit chitosanase specificity and propose additional determinants for their classification.
- Tobias Weikert
- , Anna Niehues
- & Bruno M. Moerschbacher
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Article
| Open AccessAnomeric memory of the glycosidic bond upon fragmentation and its consequences for carbohydrate sequencing
Establishing generic carbohydrate sequencing methods is both a major scientific challenge and a strategic priority. Here the authors show a hybrid analytical approach integrating molecular spectroscopy and mass spectrometry to resolve carbohydrate isomerism, anomeric configuration, regiochemistry and stereochemistry.
- Baptiste Schindler
- , Loïc Barnes
- & Isabelle Compagnon