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| Open AccessStructural insights into photosystem II supercomplex and trimeric FCP antennae of a centric diatom Cyclotella meneghiniana
The cryo-EM structures of an FCP trimer and a PSII-FCPII supercomplex from a diatom are revealed, providing detailed insights into the variety of FCPII and their regulatory roles in green light harvesting, energy transfer and dissipation.
- Songhao Zhao
- , Lili Shen
- & Wenda Wang
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Article
| Open AccessUnravelling the mechanism of neurotensin recognition by neurotensin receptor 1
GPCRs include inactive and active states. 19F-NMR and stopped-flow fluorescence kinetic assays reveal that neurotensin activates the prototypical peptide-binding GPCR, neurotensin receptor 1, through an induced-fit mechanism, where ligand binding precedes receptor conformational changes.
- Kazem Asadollahi
- , Sunnia Rajput
- & Paul R. Gooley
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Article
| Open AccessStructural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family
Cryo-EM structures of the polymerase of Tilapia Lake virus (Amnoonviridae), a fish pathogen, show that it has the same domains and functions similarly to the distantly related influenza virus (Orthomyxoviridae) polymerase, despite being only 60% the size.
- Benoit Arragain
- , Martin Pelosse
- & Stephen Cusack
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Article
| Open AccessStructures of human prostaglandin F2α receptor reveal the mechanism of ligand and G protein selectivity
Cryo-EM structures reveal the molecular mechanism of ligands and G protein selectivity for prostaglandin F2α receptor, providing guidance for development of better postpartum hemorrhage drugs.
- Xiuqing Lv
- , Kaixuan Gao
- & Xiangyu Liu
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Article
| Open AccessStructure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex
In this study, the authors present the cryogenic electron microscopy reconstruction of the Rpd3S complex engaged with a nucleosome. The corresponding model describes the interactions that facilitate histone deacetylation within gene bodies by the Rpd3S complex.
- Jonathan W. Markert
- , Seychelle M. Vos
- & Lucas Farnung
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| Open AccessStructural and thermodynamic insights into antibody light chain tetramer formation through 3D domain swapping
Atomic-level structural examinations of antibody light chain aggregates are sparse. Here, the authors find an antibody light chain that maintains an equilibrium between monomeric and tetrameric states and show with its 3D structure that it engages in 3D domain swapping within its variable region.
- Takahiro Sakai
- , Tsuyoshi Mashima
- & Shun Hirota
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Article
| Open AccessUnderstanding the molecular mechanisms of odorant binding and activation of the human OR52 family
Limited insight existed on human odorant receptors (ORs). Here, the authors present structures of consensus OR52 in its inactive and active forms, shedding light on the activation mechanism of the OR52 family.
- Chulwon Choi
- , Jungnam Bae
- & Hee-Jung Choi
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Article
| Open AccessAtg18 oligomer organization in assembled tubes and on lipid membrane scaffolds
In this work, the authors determined the cryo-EM structures of autophagy-related protein 18 organized in helical tubes and provide insights into the molecular framework for the positioning of downstream components of the autophagy machinery.
- Daniel Mann
- , Simon A. Fromm
- & Carsten Sachse
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Article
| Open AccessRegulation of the cell division hydrolase RipC by the FtsEX system in Mycobacterium tuberculosis
Here, the authors use cryo-EM and biochemical approaches to characterise the structure and interactions of the FtsEX complex in Mycobacterium tuberculosis. The results show that FtsEX engages RipC in a unique way through a “Match and Fit” mechanism.
- Jianwei Li
- , Xin Xu
- & Min Luo
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Article
| Open AccessA structure of the relict phycobilisome from a thylakoid-free cyanobacterium
Phycobilisomes are megacomplexes in cyanobacteria that capture light. Here, authors characterize a relict paddle-shaped phycobilisome structure, revealing phycobilisome diversity prior to the development of thylakoids.
- Han-Wei Jiang
- , Hsiang-Yi Wu
- & Ming-Yang Ho
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Article
| Open AccessTargeted mutagenesis of the herpesvirus fusogen central helix captures transition states
The early stages of viral fusogen conformational change required for enveloped viruses to infect cells is unclear. Here, authors capture the herpesvirus fusogen, glycoprotein B, in early transitional states by cryo-EM.
- Momei Zhou
- , Benjamin Vollmer
- & Stefan L. Oliver
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Article
| Open AccessInsights into the ISG15 transfer cascade by the UBE1L activating enzyme
Interferon stimulated gene 15 (ISG15) is a ubiquitin-like protein with critical roles in the innate immune response. Here, the authors present a Cryo-EM structure of ISG15 in complex with its E1 and E2 enzymes, providing insights into the specificity determinants of this pathway.
- Iona Wallace
- , Kheewoong Baek
- & Kirby N. Swatek
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Article
| Open AccessA multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers
Protein serial crystallography at X-ray free-electron lasers (XFELs) is a powerful technique for structure determination. Here, authors present a device for sample delivery designed to abate challenges to non-specialists allowing for compound screening.
- Maximilian Wranik
- , Michal W. Kepa
- & Jörg Standfuss
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Article
| Open AccessStructural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome
The biogenesis of ribosomes is a highly coordinated process. Here, Nguyen et al. uncover how the mitochondria-specific interplay of the GTPases GTPBP10 and GTPBP7 ensures proper maturation of the catalytic RNA center of the human mitoribosome.
- Thu Giang Nguyen
- , Christina Ritter
- & Eva Kummer
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Article
| Open AccessAssembly mechanism of the inflammasome sensor AIM2 revealed by single molecule analysis
Mechanistic insight into inflammasome formation is important for designing anti-inflammatory interventions. Here, the authors reveal the kinetics and distinct assembly modes of the early stages of the AIM2 inflammasome that detects pathogenic DNA.
- Meenakshi Sharma
- & Eva de Alba
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Article
| Open AccessStructural basis of a redox-dependent conformational switch that regulates the stress kinase p38α
p38α is a kinase that regulates many cellular processes. Here authors report that redox fluctuations induce conformational changes to fine-tune the p38α activity beyond its activation loop phosphorylation.
- Joan Pous
- , Blazej Baginski
- & Maria J. Macias
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Article
| Open AccessPyroptosis inhibiting nanobodies block Gasdermin D pore formation
Pyroptosis has been implicated in many diseases with aberrant inflammation. Here, Kopp et al. characterize single-chain nanobodies targeting the human gasdermin D protein as tools to inhibit pyroptosis.
- Anja Kopp
- , Gregor Hagelueken
- & Matthias Geyer
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Article
| Open AccessStructural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8
CCR8 is a promising target in cancer immunotherapy. Here, authors generated mAb1, an antagonist antibody against CCR8 and determined structures of CCR8 in complex with mAb1 or the agonist CCL1, providing insights into CCR8 inhibition and activation.
- Dawei Sun
- , Yonglian Sun
- & Matthieu Masureel
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Article
| Open AccessSARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle
Coronavirus RNA replication is governed by membrane vesicles containing pores. The authors used in situ cryo-electron tomography to reveal the minimal constituents of a SARS-CoV-2 “replicopore” and its role in the formation of replication vesicles.
- Liv Zimmermann
- , Xiaohan Zhao
- & Petr Chlanda
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Article
| Open AccessDistinct activation mechanisms of β-arrestin-1 revealed by 19F NMR spectroscopy
The molecular basis for the functional versatility of β-arrestins in the G-protein coupled receptor signaling pathway is not well understood. Here, the authors use19F NMR spectroscopy to show that different binding partners activate β-arrestin-1 through distinct mechanisms.
- Ruibo Zhai
- , Zhuoqi Wang
- & Yunfei Hu
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Article
| Open AccessIlluminating the mechanism and allosteric behavior of NanoLuc luciferase
NanoLuc luciferase is a popular bioluminescent enzyme, but the molecular details of its mechanism of action on luciferins such as coelenterazine remained elusive. Here the authors use, protein crystal structures and biochemical analyses to provide an atomistic description of its catalytic mechanism and allosteric behaviour.
- Michal Nemergut
- , Daniel Pluskal
- & Martin Marek
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Article
| Open AccessUnexpected dynamics in femtomolar complexes of binding proteins with peptides
High binding affinities are usually obtained when ligands are rigidified. Here the authors present flexible peptides binding to Armadillo repeat proteins with femtomolar affinity. They demonstrate that the bound state is characterized by residual dynamics limiting entropic losses upon binding.
- Stefano Cucuzza
- , Malgorzata Sitnik
- & Oliver Zerbe
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Article
| Open AccessStructural and functional insights into the delivery of a bacterial Rhs pore-forming toxin to the membrane
Bacterial Rhs proteins constitute a diverse family of secreted toxins. Here, the authors present a cryo-electron microscopy structure of an Rhs protein from Pseudomonas aeruginosa and provide insights into the mechanisms by which the protein delivers its encapsulated pore-forming toxin fragment to the bacterial membrane.
- Amaia González-Magaña
- , Igor Tascón
- & David Albesa-Jové
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Article
| Open AccessLipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins
Interpretation of lipid-like densities in cryo-EM structures of membrane proteins is challenging. Here authors present LipIDens, enabling molecular dynamics analysis of protein-lipid interactions.
- T. Bertie Ansell
- , Wanling Song
- & Mark S. P. Sansom
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Article
| Open AccessMolecular basis for the catalytic mechanism of human neutral sphingomyelinases 1 (hSMPD2)
Neutral sphingomyelinases play pivotal roles in ceramide-related signaling transduction. Here, the authors solve the structure of human neutral sphingomyelinase SMPD2 and propose a catalytic mechanism, potentially enhancing understanding of ceramide in disease and cancer treatment.
- Jingbo Yi
- , Boya Qi
- & Maojun Yang
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Article
| Open AccessDiscovery of a non-canonical prototype long-chain monoacylglycerol lipase through a structure-based endogenous reaction intermediate complex
Here, the authors present the structure of an orphan lipase in complex with an endogenous C18 monoacylglycerol ester reaction intermediate derived from the expression host, which along with enzymatic assays enabled functional assignment as a prototypical long-chain monoacylglycerol lipase.
- Nikos Pinotsis
- , Anna Krüger
- & Matthias Wilmanns
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Article
| Open AccessStochastic chain termination in bacterial pilus assembly
Adhesive type-1 pili from Escherichia coli are filamentous protein complexes consisting of a short tip and a long rod formed by up to several thousand copies of a major subunit. Here, Giese et al. reconstitute the entire type-1 pilus rod assembly reaction in vitro, using all constituent protein subunits, and identify a subunit that acts as an irreversible assembly terminator.
- Christoph Giese
- , Chasper Puorger
- & Rudi Glockshuber
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Article
| Open AccessCommon transthyretin-derived amyloid fibril structures in patients with hereditary ATTR amyloidosis
Hereditary ATTR amyloidosis has diverse disease manifestations. Using cryo-EM it was possible to reveal, that the phenotypic variations arise from the circumstances under which the amyloid fibrils are formed, rather than from different fibril morphologies.
- Maximilian Steinebrei
- , Julian Baur
- & Marcus Fändrich
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Article
| Open AccessStructure of the DDB1-AMBRA1 E3 ligase receptor complex linked to cell cycle regulation
AMBRA1 functions as a substrate receptor for E3 ubiquitin ligase complexes to promote ubiquitination and degradation of Cyclin D. Here the authors demonstrated the structure of AMRBA1 in complex with DDB1. Disruption of intermolecular interactions caused deregulation of cell cycle and DNA damage repair.
- Ming Liu
- , Yang Wang
- & Goran Stjepanovic
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Article
| Open AccessOrthosteric and allosteric modulation of human HCAR2 signaling complex
Hydroxycarboxylic acid receptor 2 (HCAR2) has been implicated in cardiovascular and neuroinflammatory diseases. Here, the authors present cryo-EM structures of HCAR2-Gi1 complexes bound to different ligands and provide insights into the mechanisms of both orthosteric and allosteric modulation of HCAR2.
- Chunyou Mao
- , Mengru Gao
- & Yan Zhang
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Article
| Open AccessStructure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus
To read and transcribe the viral genome, the polymerase complex of human metapneumovirus (HMPV) needs to attach to the nucleocapsid. Here, the authors define the dynamic basis of how the polymerase cofactor P facilitates this attachment.
- Jack D. Whitehead
- , Hortense Decool
- & Max Renner
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Article
| Open AccessMyr-Arf1 conformational flexibility at the membrane surface sheds light on the interactions with ArfGAP ASAP1
An integrated approach combing solution and solid-state NMR, molecular dynamics simulations and neutron reflectometry is applied to characterize dynamic membrane bound forms of ADP-ribosylation factor 1 (Arf1).
- Yue Zhang
- , Olivier Soubias
- & R. Andrew Byrd
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Article
| Open AccessStructure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry
TMPRSS2 and CTSL/CTSB, host proteases that facilitate SARS-CoV-2 entry, are promising drug targets. Here the authors simultaneously inhibit these host proteases and see synergistic antiviral effects, offering a broad-spectrum intervention against SARS-CoV-2 variants.
- Haofeng Wang
- , Qi Yang
- & Haitao Yang
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Article
| Open AccessThe structure of the teleost Immunoglobulin M core provides insights on polymeric antibody evolution, assembly, and function
The formation of polymeric Ig complexes is important for the function of IgM and can vary between species. Here the authors structurally analyse IgM from a teleost species that doesn’t encode a joining chain, which results in a different 3D structure compared to mammalian IgM where other parts of the protein associate to form polymeric complexes.
- Mengfan Lyu
- , Andrey G. Malyutin
- & Beth M. Stadtmueller
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Article
| Open AccessStructures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant
Interleukin (IL-)11 is a signaling protein that plays key roles in several human diseases. Here the authors describe structures of IL-11 in complex with its receptors and determine the molecular mechanisms through which a variant of IL-11 inhibits signalling, opening avenues for therapeutic development.
- Riley D. Metcalfe
- , Eric Hanssen
- & Michael D. W. Griffin
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Article
| Open AccessArchitecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly
The soluble neurotrophic factor GDNF promotes trans-synaptic adhesion through its co-receptor GFRα1. Here, the authors describe the structural basis for GDNF-GFRα1 adhesion and reconstitute assemblies bridging membranes, demonstrating that binding of either the RET receptor or proteoglycans can disrupt this adhesive function.
- F. M. Houghton
- , S. E. Adams
- & N. Q. McDonald
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Article
| Open AccessMembrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT
Sodium glucose transporters are critical for maintaining glucose homeostasis. Here, authors provide a detailed framework for how SGLTs utilize cellular membrane potentials to stabilize their substrate accepting conformation leading to accelerated transport.
- Farha Khan
- , Matthias Elgeti
- & Jeff Abramson
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Article
| Open AccessArchitecture of the baculovirus nucleocapsid revealed by cryo-EM
Baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is used as a bioinsecticide and a protein expression vector. Here, the authors report structures of cylindrical body of the AcMNPV nucleocapsid, as well as of both the nucleocapsid head and base.
- Xudong Jia
- , Yuanzhu Gao
- & Qinfen Zhang
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Article
| Open AccessActivation and substrate specificity of the human P4-ATPase ATP8B1
Asymmetric phospholipid distribution in cell membranes is vital for cellular function. Here, authors reveal how ATP8B1, a P4-ATPase, can transport different lipids, including phosphatidylinositol.
- Thibaud Dieudonné
- , Felix Kümmerer
- & Poul Nissen
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Article
| Open AccessSerine peptidase Vpr forms enzymatically active fibrils outside Bacillus bacteria revealed by cryo-EM
Here, cryo-EM is used to identify an unreported fibril species derived from lab-cultured Bacillus amyloiquefaciens composed of the extracellular serine peptidase Vpr. Fibrillar Vpr is shown to be enzymatically active, suggesting the fibril form represents a strategy of enriching Vpr extracellular activity.
- Yijia Cheng
- , Jianting Han
- & Qin Cao
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Article
| Open AccessA tradeoff between enterovirus A71 particle stability and cell entry
Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. Here, the authors show that a single mutation in enterovirus A71 capsid affects the balance between particle stability and cell entry efficiency. Structural and simulation analyses reveal an expanded conformation in the thermostable viruses, resulting in increased particle flexibility.
- Adam Catching
- , Ming Te Yeh
- & Raul Andino
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Article
| Open AccessUnconventional structure and mechanisms for membrane interaction and translocation of the NF-κB-targeting toxin AIP56
Structural and functional characterization of an NF-κB-targeting bacterial toxin reveals an unconventional structure and mechanisms of membrane interaction and translocation.
- Johnny Lisboa
- , Cassilda Pereira
- & Nuno M. S. dos Santos
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Article
| Open AccessProRefiner: an entropy-based refining strategy for inverse protein folding with global graph attention
Inverse Protein Folding is a critical component of protein design. Here, authors introduce ProRefiner, a deep-learning model for IPF that exhibits both high performance and memory efficiency, thereby contributing to advancements in protein design.
- Xinyi Zhou
- , Guangyong Chen
- & Pheng Ann Heng
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Article
| Open AccessThe structural and functional investigation into an unusual nitrile synthase
The nitrile synthase AetD is a crucial component in the biosynthetic pathway of neurotoxin aetokthonotoxin (AETX). Here, the authors solved crystal structures of AetD in complex with different substrates, revealing that AetD represents a new type of HO-like diiron enzyme and the possibility of expanding its substrate spectrum.
- Hao Li
- , Jian-Wen Huang
- & Chun-Chi Chen
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Article
| Open AccessStructural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
T-box riboswitches are RNA-based gene regulators, composed of highly structured noncoding RNAs: the T-box and a tRNA ligand. Here, the authors assess the folding of a translational T-box aptamer and dissect the role of Mg2+, intra- and intermolecular RNA-RNA interactions in modulating its folding and function.
- Xiaolin Niu
- , Zhonghe Xu
- & Xianyang Fang
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Article
| Open AccessM. mazei glutamine synthetase and glutamine synthetase-GlnK1 structures reveal enzyme regulation by oligomer modulation
Glutamine synthetases (GS) play vital roles in cellular nitrogen assimilation and hence these enzymes, which form large oligomeric machines, are tightly regulated. Here the authors reveal the molecular mechanism behind a unique form of GS regulation involving oligomer modulation.
- Maria A. Schumacher
- , Raul Salinas
- & Nicholas Lent
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Article
| Open AccessThe GET insertase exhibits conformational plasticity and induces membrane thinning
Tail-anchored (TA) membrane protein biogenesis is mediated by the GET insertase. Here, authors present cryo-EM and X-ray structures, MD simulations and functional data for human and fungal insertases showing membrane remodeling for TA insertion.
- Melanie A. McDowell
- , Michael Heimes
- & Irmgard Sinning
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Article
| Open AccessCryo-EM structures of the plant anion channel SLAC1 from Arabidopsis thaliana suggest a combined activation model
Phosphorylation-mediated activation of SLAC1 anion channel is crucial in plant responses for abiotic stresses including drought. Here, authors determine the open and closed structures of SLAC1, revealing how phosphorylation can activate SLAC1.
- Yeongmok Lee
- , Hyeon Seong Jeong
- & Sangho Lee
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Article
| Open AccessMechanistic insights into glycoside 3-oxidases involved in C-glycoside metabolism in soil microorganisms
Integrated experimental and computational approaches reveal functional and structural details of a key catabolic enzyme that oxidizes recalcitrant C-glycosides, abundant and biologically significant natural molecules, before deglycosylation.
- André Taborda
- , Tomás Frazão
- & Lígia O. Martins