Enzyme mechanisms articles within Nature Communications

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  • 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

  • Article
    | Open Access

    Squalene epoxidase (SQLE) is a key enzyme in cholesterol biosynthesis and is a target for hypercholesteremia and cancer drug development. Here the authors present the crystal structures of the human SQLE catalytic domain alone and bound with small molecule inhibitors, which will facilitate the development of next-generation SQLE inhibitors.

    • Anil K. Padyana
    • , Stefan Gross
    •  & Gromoslaw A. Smolen

  • Article
    | Open Access

    The maintenance polyamines homeostasis is important for cell growth, and several cancers harbor elevated levels of polyamines that may contribute to sustained proliferative potential. Here the authors demonstrate that polyamines participate in DNA double-strand break repair through the stimulation of RAD51-mediated homologous DNA pairing and strand exchange.

    • Chih-Ying Lee
    • , Guan-Chin Su
    •  & Peter Chi

  • Article
    | Open Access

    Alkaline ceramidases (ACERs) are a class of poorly understood transmembrane enzymes controlling the homeostasis of ceramides. Here authors solve the Xray structure of human ACER3 and uncover a Ca2+ binding site providing an explanation for the known regulatory role of Ca2+ on ACER3 activity.

    • Ieva Vasiliauskaité-Brooks
    • , Robert D. Healey
    •  & Sébastien Granier

  • Article
    | Open Access

    Ubiquitin and ubiquitin-like modifiers such as SUMO play important roles in several cellular pathways that can become deregulated in cancer. Here the authors describe the structural basis for inhibition of SUMO E1 ligase by the small molecule COH000.

    • Zongyang Lv
    • , Lingmin Yuan
    •  & Shaun K. Olsen

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase, which requires the leading-strand polymerase Pol ɛ. Here the authors present a structural analysis of a CMG Pol ɛ on a DNA fork, providing insight on the steps leading productive helicase engagement to the DNA junction.

    • Panchali Goswami
    • , Ferdos Abid Ali
    •  & Alessandro Costa

  • Article
    | Open Access

    Efficient biosynthesis of lactams is still undesirable due to lacking of suitable enzyme. Here, the authors develop a sensitive transcription factor-based biosensor for high-throughput screening of marine metagenome and find a cyclase that can cyclize ω-amino fatty acids to lactam.

    • Soo-Jin Yeom
    • , Moonjeong Kim
    •  & Seung-Goo Lee

  • Article
    | Open Access

    Topoisomerases solve topological problems during DNA metabolism, but their role in RNA metabolism remains unclear. Here the authors provide evidence that in Drosophila, Topoisomerase 3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) to promote heterochromatin formation and transcriptional silencing.

    • Seung Kyu Lee
    • , Yutong Xue
    •  & Weidong Wang

  • Article
    | Open Access

    Soluble fumarate reductases are essential for eukaryotic cell survival under anaerobic conditions but their mechanism is not fully understood. Here, the authors present structural and enzymatic analyses of yeast fumarate reductase Osm1, elucidating the molecular basis of maintaining redox balance during anaerobiosis.

    • Sunghwan Kim
    • , Chang Min Kim
    •  & Hyun Ho Park

  • Article
    | Open Access

    [FeFe]-hydrogenases catalyze H2-evolution and -oxidation at very high turnover-rates. Here the authors provide experimental evidence for the proposed proton-transfer (PT) pathway by kinetically, spectroscopically, and crystallographically characterizing eleven mutants from the two [FeFe]-hydrogenases CpI and HydA1.

    • Jifu Duan
    • , Moritz Senger
    •  & Martin Winkler

  • Article
    | Open Access

    The activity of several protein kinases is increased upon cellular production of reactive oxygen species, which can cause cysteine oxidation. Here the authors show that sulfenylation of specific cysteine residues within Src induce local structural changes that directly impact its activation.

    • David E. Heppner
    • , Christopher M. Dustin
    •  & Albert van der Vliet

  • Article
    | Open Access

    The protein tyrosine phosphatase SHP2 is a key regulator of cell cycle control. Here the authors combine NMR measurements and X-ray crystallography and show that wild-type SHP2 dynamically exchanges between a closed inactive conformation and an open activated form and that the oncogenic E76K mutation shifts the equilibrium to the open state, which is reversed by binding of the allosteric inhibitor SHP099.

    • Ricardo A. P. Pádua
    • , Yizhi Sun
    •  & Dorothee Kern

  • Article
    | Open Access

    The NDM-1 β-lactamase confers resistance to most β-lactam antibiotics. By functional analysis of residues required for hydrolysis, Sun et al. reveal stringent sequence constraints for carbapenems, suggesting that specific combinations of NDM-1 inhibitors might help reducing resistance development

    • Zhizeng Sun
    • , Liya Hu
    •  & Timothy Palzkill

  • Article
    | Open Access

    Proton pumping of mitochondrial complex I depends on the reduction of ubiquinone but the molecular mechanism of energy conversion is unclear. Here, the authors provide structural and biochemical evidence showing that movement of loop TMH1-2 in complex I subunit ND3 is required to drive proton pumping.

    • Alfredo Cabrera-Orefice
    • , Etienne Galemou Yoga
    •  & Ulrich Brandt

  • Article
    | Open Access

    Ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein that hydrolyzes both ATP and cGAMP. Here the authors present the crystal structures of the extracellular domain of mouse ENPP1 in complex with 3′3′-cGAMP and the reaction intermediate pA(3′,5′)pG and discuss mechanistic implications.

    • Kazuki Kato
    • , Hiroshi Nishimasu
    •  & Osamu Nureki

  • Article
    | Open Access

    Metal ions at the active site of an enzyme act as cofactors and their dynamic fluctuations might influence enzyme activity. Here authors use single-molecule FRET to study λ-exonuclease and find that metal-ion-coordination is correlated with enzymatic reaction-steps.

    • Wonseok Hwang
    • , Jungmin Yoo
    •  & Gwangrog Lee

  • Article
    | Open Access

    Enzymes of the six-transmembrane epithelial antigen of the prostate (STEAP) family reduce Fe3+ and Cu2+ ions to facilitate metal-ion uptake by mammalian cells. Here, authors employ single-particle cryo-EM to gain insights into the molecular principles of iron reduction by human STEAP4 .

    • Wout Oosterheert
    • , Laura S. van Bezouwen
    •  & Piet Gros

  • Article
    | Open Access

    How G-quadruplexes (G4s) are resolved by helicases is still a matter of investigation. Here the authors provide mechanistic insight into G4s unwinding by presenting a crystal structure of resolved G4 DNA and the G4 binding domain of RecQ helicase from the bacterium Cronobacter sakazakii.

    • Andrew F. Voter
    • , Yupeng Qiu
    •  & James L. Keck

  • Article
    | Open Access

    It has previously been established that DNA end resection in yeast and in humans is under CDK control. Here the authors explain how phosphorylation regulates the capacity of Sae2 — the yeast orthologue of human CtIP — to promote DNA end resection.

    • Elda Cannavo
    • , Dominic Johnson
    •  & Petr Cejka

  • Article
    | Open Access

    The bacterial diterpene synthase CotB2 catalyses the cyclisation of geranylgeranyl diphosphate to cyclooctat-9-en7-ol. Here the authors present various CotB2 structures including a trapped abrupt reaction product that were used for molecular dynamic simulations and allowed them to model all intermediates along the reaction cascade.

    • Ronja Driller
    • , Sophie Janke
    •  & Bernhard Loll

  • Article
    | Open Access

    The monoamine oxidase family member LkcE is an enzyme from the lankacidin polyketide biosynthetic pathway, where it catalyzes an amide oxidation followed by an intramolecular Mannich reaction, yielding the polyketide macrocycle. Here the authors characterize LkcE and present several of its crystal structures, which explains the unusual dual activity of LkcE.

    • Jonathan Dorival
    • , Fanny Risser
    •  & Kira J. Weissman

  • Article
    | Open Access

    The cellular toxicity of Pseudomonas exotoxin-S and -T depends on their activation by 14-3-3 but the underlying molecular mechanism is not fully understood. Here, the authors show that a previously unrecognized 14-3-3:exotoxin binding interface is sufficient for complex formation and toxin activation.

    • Tobias Karlberg
    • , Peter Hornyak
    •  & Herwig Schüler

  • Article
    | Open Access

    UPF1 is a highly processive helicase that plays an essential role in nonsense-mediated mRNA decay. Here the authors use single molecule binding assays to establish a functionally important relationship between helicase grip to nucleic acids, binding lifetime and the duration of translocation.

    • Joanne Kanaan
    • , Saurabh Raj
    •  & Hervé Le Hir

  • Article
    | Open Access

    The natural products fosfazinomycin A and kinamycin D are structurally distinct except for a nitrogen-nitrogen (N-N) bond. Here, the authors show that fosfazinomycin and kinamycin share a common pathway for N-N bond formation that is different from pathways found for other natural products.

    • Kwo-Kwang A. Wang
    • , Tai L. Ng
    •  & Wilfred A. van der Donk

  • Article
    | Open Access

    Eukaryotic elongation factor 1 alpha (eEF1A) is subject to extensive post-translational methylation but not all responsible enzymes are known. Here, the authors identify METTL13 as an eEF1A methyltransferase with dual specificity, which is involved in the codon-specific modulation of mRNA translation.

    • Magnus E. Jakobsson
    • , Jędrzej M. Małecki
    •  & Pål Ø. Falnes

  • Article
    | Open Access

    INO80 chromatin remodeler plays important roles in transcription, DNA repair, recombination, and heterochromatin maintenance. Here the authors characterise the functional interplay between the actin-related proteins (Arps)  in INO80, showing that Arp8 and Arp4 module sense the DNA length separating nucleosomes and regulate nucleosome remodeling.

    • Sandipan Brahma
    • , Mzwanele Ngubo
    •  & Blaine Bartholomew

  • Article
    | Open Access

    The circadian clock proteins KaiA, KaiB, and KaiC reconstitute a circa-24 h oscillation of KaiC phosphorylation in vitro. Here the authors use high-speed atomic force microscopy to visualize in real time and quantify the dynamic interactions of KaiA with KaiC on the sub-second timescale to discover mechanisms of oscillatory resilience.

    • Tetsuya Mori
    • , Shogo Sugiyama
    •  & Toshio Ando

  • Article
    | Open Access

    Cytochrome c oxidase (CytcO) is the last enzyme of the electron transport chain, but how the electrochemical membrane potential affects CytcO is unclear. Here the authors show that proton uptake to the catalytic site of CytcO and presumably proton translocation was impaired by the potential, but electron transfer was not affected.

    • Markus L. Björck
    •  & Peter Brzezinski

  • Article
    | Open Access

    Viridicatin is a fungal alkaloid. Here, the authors identify and characterize the cyclopenase that catalyzes the last step of its biosynthesis in Aspergillus nidulans, the conversion of cyclopenin to viridicatin, and find that the reaction proceeds via an unusual elimination mechanism.

    • Shinji Kishimoto
    • , Kodai Hara
    •  & Kenji Watanabe

  • Article
    | Open Access

    The biosynthesis of the antitumour antibiotic CC-1065 includes formation of a cyclopropane. Here, the authors identify the two enzymes that work together to catalyze this reaction, a radical S-adenosyl-l-methionine enzyme and a methyltransferase, and propose a mechanism for the cyclopropanation.

    • Wen-Bing Jin
    • , Sheng Wu
    •  & Gong-Li Tang

  • Article
    | Open Access

    Catabolizing lignin-derived aromatic compounds requires an aryl-O-demethylation step. Here the authors present the structures of GcoA and GcoB, a cytochrome P450-reductase pair that catalyzes aryl-O-demethylations and show that GcoA displays broad substrate specificity, which is of interest for biotechnology applications.

    • Sam J. B. Mallinson
    • , Melodie M. Machovina
    •  & John E. McGeehan

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