Enzyme mechanisms articles within Nature Communications

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  • Article
    | Open Access

    Respiratory syncytial virus (RSV) is a pathogenic non-segmented negative-sense RNA virus and active RSV polymerase is composed of a 250 kDa large (L) protein and tetrameric phosphoprotein (P). Here, the authors present the 3.67 Å cryo-EM structure of the RSV polymerase (L:P) complex.

    • Dongdong Cao
    • , Yunrong Gao
    •  & Bo Liang

  • Article
    | Open Access

    DNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. Here the authors present X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA that unveil determinants of LIG1 substrate recognition and enzymatic fidelity.

    • Percy P. Tumbale
    • , Thomas J. Jurkiw
    •  & R. Scott Williams

  • Article
    | Open Access

    Cytochrome bd oxidases couple quinol oxidation and the release of protons to the periplasmic side with proton uptake from the cytoplasmic side to reduce dioxygen to water and they are the terminal reductases in bacterial and archaeal respiratory chains. Here the authors present the cryo-EM structure of Escherichia coli bd oxidase and discuss mechanistic implications.

    • Alexander Theßeling
    • , Tim Rasmussen
    •  & Thorsten Friedrich

  • Article
    | Open Access

    Bacterial DNA gyrase is the only type II DNA topoisomerase capable of introducing negative supercoils into DNA and is of interest as a drug target. Here the authors present the cryo-EM structure of the complete E. coli DNA gyrase bound to a 180 bp double-stranded DNA and the antibiotic gepotidacin, which reveals the connections between the functional domains and their spatial organization.

    • Arnaud Vanden Broeck
    • , Christophe Lotz
    •  & Valérie Lamour

  • Article
    | Open Access

    Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Here, authors report crystal structures of truncated human MFN2 in different nucleotide-loading states and show that MFN2 forms sustained dimers even after GTP hydrolysis.

    • Yu-Jie Li
    • , Yu-Lu Cao
    •  & Song Gao

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Retroviral integration of DNA into the host genome is a point of no return in the replication cycle but how efficient integration can take place remains unclear. Here the authors demonstrate that consecutive nucleoprotein intermediates are increasingly stable, resulting in a net forward rate.

    • Willem Vanderlinden
    • , Tine Brouns
    •  & Jan Lipfert

  • Article
    | Open Access

    Isocitrate lyase (ICL) isoforms 1 and 2 are enzymes in the glyoxylate and methylcitrate cycles that enable Mycobacterium tuberculosis (Mtb) to use lipids as a carbon source. Here the authors present the ligand-free Mtb ICL2 and acetyl-CoA bound ICL2 crystal structures, which reveal a structural reorganisation upon acetyl-CoA binding that leads to an activation of its isocitrate lyase and methylcitrate lyase activities.

    • Ram Prasad Bhusal
    • , Wanting Jiao
    •  & Ivanhoe K. H. Leung

  • Article
    | Open Access

    CcrM is a cell cycle-regulated DNA methyltransferase that methylates an adenine within a specific sequence following replication in the gram negative bacterium Caulobacter crescentus. Here the authors present a crystal structure of DNA-bound CcrM that reveals the molecular mechanism leading to sequence-specific methylation.

    • John R. Horton
    • , Clayton B. Woodcock
    •  & Xiaodong Cheng

  • Article
    | Open Access

    Aldehyde-alcohol dehydrogenase (AdhE) converts acetyl-CoA to ethanol and plays an important role in bacterial fermentation. Here the authors present the 3.5 Å cryo-EM structure of full-length E. coli AdhE, which reveals a right-handed helical spirosome structure and they show that the helical structure is required for AdhE activity.

    • Gijeong Kim
    • , Liyana Azmi
    •  & Ji-Joon Song

  • Article
    | Open Access

    FAT10 is an ubiquitin-like modifier that targets proteins to proteasomal degradation. Here, the authors show that FAT10 also regulates SUMO activation in vitro and in cells, providing evidence for functional crosstalk between two ubiquitin-like modifiers.

    • Annette Aichem
    • , Carolin Sailer
    •  & Marcus Groettrup

  • Article
    | Open Access

    Retroviral integrases catalyze the insertion of viral DNA into the host cell DNA and can use nucleosomes as substrates for integration. Here the authors present the 3.9 Å cryo-EM structure of prototype foamy virus integrase after strand transfer into nucleosomal DNA, which together with single-molecule FRET measurements provides evidence for a DNA looping and sliding mechanism of integrases.

    • Marcus D. Wilson
    • , Ludovic Renault
    •  & Alessandro Costa

  • Article
    | Open Access

    NocTE is a nonribosomal peptide synthetase thioesterase that completes the biosynthesis of pro-nocardicin G, the precursor for nocardicin β-lactam antibiotics. Here the authors provide mechanistic insights into NocTE by determining its crystal structures in the ligand-free form and covalently linked to a fluorophosphonate substrate mimic.

    • Ketan D. Patel
    • , Felipe B. d’Andrea
    •  & Andrew M. Gulick

  • Article
    | Open Access

    The COP9 signalosome (CSN) regulates Cullin-RING Ligase 2 (CRL2) but the molecular basis for their interaction is unknown. Here the authors use structural mass spectrometry and cryo-EM approaches to assess the structures and dynamics of CSN-CRL2 complexes.

    • Sarah V. Faull
    • , Andy M. C. Lau
    •  & Argyris Politis

  • Article
    | Open Access

    Amine dehydrogenases (AmDHs) catalyse the conversion of ketones into amines. Here, the authors created AmDH variants, the best of which showing a substrate-dependent stereo-switchable selectivity, affording either S- or R-configured amine products with up to >99.9% enantiomeric excess.

    • Vasilis Tseliou
    • , Tanja Knaus
    •  & Francesco G. Mutti

  • Article
    | Open Access

    During a process termed synapsis, the two DNA ends at a double-strand break (DSB) are brought together into physical proximity. Here, the authors use a single-molecule FRET approach with purified proteins to investigate the mechanism of synapsis in DSB repair by non-homologous DNA end joining (NHEJ).

    • Bailin Zhao
    • , Go Watanabe
    •  & Michael R. Lieber

  • Article
    | Open Access

    Autophagy mediated by the conjugation pathway for ubiquitin-like proteins plays a key role in controlling homeostasis in eukaryotic cells. Here the authors provide a molecular basis for allosteric activation of the E2 ligase Atg3, uncovering the mechanism underlying Atg8 lipidation and a novel mechanism regulating E1-E2-E3-mediated ubiquitin-like protein conjugation.

    • Yumei Zheng
    • , Yu Qiu
    •  & Brenda A. Schulman

  • Article
    | Open Access

    The mechanism of iron-sulfur (Fe-S) cluster biosynthesis is not fully understood. Here, the authors develop a physiologically relevant in vitro model of Fe-S cluster assembly, allowing them to elucidate the sequence of Fe-S cluster synthesis along with the respective roles of ferredoxin-2 and frataxin.

    • Sylvain Gervason
    • , Djabir Larkem
    •  & Benoit D’Autréaux

  • Article
    | Open Access

    How the human Alanine Serine Cysteine Transporter 2 (ASCT2) binds its substrates, neutral amino acids, and releases them on the cytoplasmic side remains unclear. Here authors present an inward-open structure of the human ASCT2 which shows that a hairpin serves as a gate in the inward-facing state.

    • Alisa A. Garaeva
    • , Albert Guskov
    •  & Cristina Paulino

  • Article
    | Open Access

    Ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxyribonucleoside diphosphates to provide dNTP precursors for DNA synthesis. Here the authors show that the availability of dNTPs, DNA replication, and cellular proliferation, are modulated by acetylation and deacetylation of RRM2 by KAT7 and Sirt2 respectively.

    • Guo Chen
    • , Yin Luo
    •  & Xingming Deng

  • Article
    | Open Access

    The VASH2/SVBP heterodimer catalyzes the detyrosination of the α-tubulin C-terminus. Here the authors provide insights into the tubulin detyrosination mechanism by determining the crystal structures of VASH2/SVBP and VASH2/SVBP in complex with a tubulin tail peptide.

    • Chen Zhou
    • , Ling Yan
    •  & Zhu Liu

  • Article
    | Open Access

    HECT type E3 ligases are key regulators of cell growth and proliferation. Here the authors present the crystal structures of the Nedd4 family E3 ligase WWP1 in a closed and semi-open state and in combination with mutagenesis experiments identify a multi-lock regulatory mechanism that allows the fine-tuning of activities of Nedd4 family E3 ligases.

    • Zhen Wang
    • , Ziheng Liu
    •  & Wenyu Wen

  • Article
    | Open Access

    DEAD-box helicases (DDXs) function in an ATP-dependent, non-processive manner and the conserved helicase core is composed of two RecA-like domains D1 and D2. Here the authors present the crystal structure of the D1D2 core from human DDX3X bound to a 23-base pair dsRNA in the pre-unwound state and discuss the implications for helicase mechanism.

    • He Song
    •  & Xinhua Ji

  • Article
    | Open Access

    McrBC is a bacterial antiphage defense system that cleaves methylated DNA and is composed of the AAA+ GTPase motor McrB and the endonuclease McrC. Here, the authors present the cryo-EM structure of E. coli McrBC that reveals how McrC inserts a stalk-like structure into the pore of the ring-shaped McrB hexamer and discuss mechanistic implications.

    • Neha Nirwan
    • , Yuzuru Itoh
    •  & Kayarat Saikrishnan

  • Article
    | Open Access

    Replication-Factor-C (RFC) and RFC-like complexes (RLCs) mediate chromatin engagement of the proliferating cell nuclear antigen (PCNA). Here authors use biochemical and single molecule measurements to show that ATAD5-RLC has the most potent PCNA unloading activity and forms structurally distinct intermediates compared to RFC-PCNA.

    • Mi-Sun Kang
    • , Eunjin Ryu
    •  & Kyungjae Myung

  • Article
    | Open Access

    Enzyme substrates and products often diffuse too rapidly to assess the catalytic implications of these movements. Here, the authors characterise the structural basis of product and substrate diffusion for an exo-hydrolase and discover a substrate-product assisted processive catalytic mechanism.

    • Victor A. Streltsov
    • , Sukanya Luang
    •  & Maria Hrmova

  • Article
    | Open Access

    Bioproduction of tetrahydropapaveroline (THP) is limited by the specificity of monoamine oxidase (MAO). Here, the authors identify an insect 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) that can bypass MAO for direct aldehyde production and demonstrate bifunctional switching of DHPAAS for efficient THP production.

    • Christopher J. Vavricka
    • , Takanobu Yoshida
    •  & Akihiko Kondo

  • Article
    | Open Access

    Plastic polymer PET degrading enzymes are of great interest for achieving sustainable plastics recycling. Here, the authors present the crystal structures of the plastic degrading bacterial enzymes PETase, MHETase in its apo-form and MHETase bound to a non-hydrolyzable substrate analog.

    • Gottfried J. Palm
    • , Lukas Reisky
    •  & Gert Weber

  • Article
    | Open Access

    Yeast’s Sen1 helicase is involved in the suppression of antisense transcription from bidirectional eukaryotic promoters. Here authors develop and utilize a quantitative single-molecule assay reporting on the kinetics of extrinsic eukaryotic transcription termination by the Sen1 helicase and a reaction intermediate in which the Pol II transcription bubble appears half-rewound.

    • S. Wang
    • , Z. Han
    •  & T. R. Strick

  • Article
    | Open Access

    The enzyme serine hydroxymethyltransferase (SHMT) has been implicated in several diseases, however is hard to investigate. Here, the authors used a design strategy based on the retro-aldol-type reaction catalyzed by SHMT to develop SHMT-responsive fluorescence and 19F NMR molecular probes.

    • Hiroshi Nonaka
    • , Yuki Nakanishi
    •  & Shinsuke Sando

  • Article
    | Open Access

    Serine/threonine phosphatases such as PP1 associate with a large array of subunit proteins, such as ASPP (apoptosis-stimulating protein of p53) to achieve selective targeting. Here authors solved the crystal structure of the human ASPP2/PP1 complex and explain how ASPP2 can distinguish between PP1 isoforms.

    • M. Teresa Bertran
    • , Stéphane Mouilleron
    •  & Nicolas Tapon

  • Article
    | Open Access

    Elp3 is the catalytic subunit of the eukaryotic Elongator complex that catalyzes posttranscriptional tRNA modifications. Here the authors present the crystal structures of an acetyl-CoA analog bound bacterial Elp3 and a monomeric archaeal Elp3 and show that Elp3 functions as a tRNA modification enzyme in all domains of life.

    • Ting-Yu Lin
    • , Nour El Hana Abbassi
    •  & Sebastian Glatt

  • Article
    | Open Access

    Little is known about the degradation pathway of cyclic imines that are frequently found in bioactive secondary metabolites. Here, the authors found and characterised a copper amine oxidase, HarA that catalyses a ring-opening reaction of cyclic imine in harmaline and oxidative deamination of amines.

    • Toshiki Nagakubo
    • , Takuto Kumano
    •  & Michihiko Kobayashi

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