Enzymes articles within Nature Communications

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  • Article
    | Open Access

    SETDB1 is a histone methyltransferase that generates H3K9me3 marks in euchromatic regions. Here the authors show that the triple Tudor domain (3TD) of SETDB1 binds histone H3 tails containing K14 acetylation combined with K9 methylation, and that the K9me–K14ac modification defines a novel chromatin state enriched at SETDB1 binding sites.

    • Renata Z. Jurkowska
    • , Su Qin
    •  & Albert Jeltsch
  • Article
    | Open Access

    Protein ADP-ribosylation has emerged as a key post translational modification that regulates several stress responses. Here the authors characterize ARH3 as a major serine-specific mono–ADP-­ribosylhydrolase and use a proteomics approach to identify the cellular targets of ARH3.

    • Jeannette Abplanalp
    • , Mario Leutert
    •  & Michael O. Hottiger
  • Article
    | Open Access

    Carminic acid is a widely applied red colorant that is still harvested from insects because its biosynthesis is not fully understood. Here, the authors identify and characterize a membrane-bound C-glucosyltransferase catalyzing the final step during carminic acid biosynthesis.

    • Rubini Kannangara
    • , Lina Siukstaite
    •  & Birger Lindberg Møller
  • Article
    | Open Access

    Drosophila Polo kinase is the founding member of the Polo-Like Kinase (PLK) family and a master regulator of mitosis and cytokinesis. Here the authors uncover a molecular mechanism for the spatiotemporal regulation of Polo kinase during mitotic entry through a phosphorylation event that triggers nuclear import.

    • David Kachaner
    • , Damien Garrido
    •  & Vincent Archambault
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Carrageenans, major cell wall polysaccharides of red macroalgae, are metabolised by marine heterotrophic bacteria through unclear mechanisms. Here, the authors identify an unusual polysaccharide-utilization locus encoding carrageenan catabolism in a marine bacterium, and characterise the complete pathway.

    • Elizabeth Ficko-Blean
    • , Aurélie Préchoux
    •  & Gurvan Michel
  • Article
    | Open Access

    The NUDIX hydrolases are known to be involved in several cellular processes and diseases, such as cancer, but remain poorly characterized as a family. Here, the authors provide a comprehensive analysis of the structural, biochemical, and expression properties of 18 human NUDIX proteins, and begin to address their functional inter-relationships.

    • Jordi Carreras-Puigvert
    • , Marinka Zitnik
    •  & Thomas Helleday
  • Article
    | Open Access

    GyrI-like proteins are small-molecule binding proteins that are widely distributed in prokaryotes and eukaryotes, with functions that are poorly characterized. Here, the authors identify GyrI-like proteins as cyclopropanoid cyclopropyl hydrolases that can confer resistance to cytotoxic cyclopropanoid compounds.

    • Hua Yuan
    • , Jinru Zhang
    •  & Gong-Li Tang
  • Article
    | Open Access

    The inner membrane assembly complex (INAC) interacts with components of the F1F0-ATP synthase but its function remains unclear. Here the authors show that INAC associates with two distinct complexes during F1F0-ATP synthase formation, which points towards a safeguarding role during proton-conducting channel assembly.

    • Nataliia Naumenko
    • , Marcel Morgenstern
    •  & Peter Rehling
  • Article
    | Open Access

    Copper-dependent lytic polysaccharide monooxygenases (LPMOs) oxidatively cleave polysaccharides. Here the authors present a structure-function characterization of fungal LPMOs, showing that a particular LPMO cleaves xylan using a mechanism that involves an alternative copper coordination geometry.

    • T. J. Simmons
    • , K. E. H. Frandsen
    •  & P. Dupree
  • Article
    | Open Access

    NADPH oxidase NOX4 has been linked to poor cancer survival. Here the authors show that NOX4 regulates drug resistance in renal cancer carcinoma by regulating PKM2 and that NOX4 activity is allosterically activated by reduced mitochondrial ATP levels thus coupling energy metabolism to drug resistance.

    • Karthigayan Shanmugasundaram
    • , Bijaya K. Nayak
    •  & Karen Block
  • Article
    | Open Access

    DNA nanostructures can cage enzymes but currently fall short of controlling their reactions with substrates. Here, the authors enclose an enzyme inside a dynamic DNA vault, which regulates its access to substrate molecules—and thus its enzymatic activity—through a multi-lock mechanism.

    • Guido Grossi
    • , Mette Dalgaard Ebbesen Jepsen
    •  & Ebbe Sloth Andersen
  • Article
    | Open Access

    The Parkinson’s disease‐associated LRRK2 protein is a multidomain Roco protein with GTPase activity. Here the authors use a multidisciplinary approach to characterize the GTPase mechanism of a homologous bacterial Roco protein and give mechanistic insights into disease-causing LRRK2 mutations.

    • Egon Deyaert
    • , Lina Wauters
    •  & Wim Versées
  • Article
    | Open Access

    BRCA proteins have emerged as key stabilizing factors for the maintenance of replication forks following replication stress. Here the authors describe how reversed replication forks are degraded in the absence of BRCA2, and a MUS81 and POLD3-dependent mechanism of rescue following the withdrawal of genotoxic agent.

    • Delphine Lemaçon
    • , Jessica Jackson
    •  & Alessandro Vindigni
  • Article
    | Open Access

    Understanding the role of enzymes in biomass depolymerization is essential for the development of more efficient biorefineries. Here, the authors show by atomic force microscopy the real-time mechanism of cellulose deconstruction by lytic polysaccharide monooxygenases.

    • Manuel Eibinger
    • , Jürgen Sattelkow
    •  & Bernd Nidetzky
  • Article
    | Open Access

    Ubiquitin ligase TRAF6 catalyzes assembly of free polyubiquitin chains for TAK1 activation in the IL-1R/TLR pathways, but the mechanism underlying its processivity is unclear. Here, the authors show that TRAF6 coiled-coil oligomerization domain primes its interaction with Ubc13/Ub~Ubc13 to confer processivity.

    • Lin Hu
    • , Jiafeng Xu
    •  & Zongping Xia
  • Article
    | Open Access

    AMPK is involved in sensing of metabolic stress. The authors show that the autophagy initiator ULK1 phosphorylates β1-Ser108 on the regulatory β1-subunit, sensitizing AMPK to allosteric drugs, and activates signaling pathways that appear independent of Thr172 phosphorylation in the kinase activation loop.

    • Toby A. Dite
    • , Naomi X. Y. Ling
    •  & Jonathan S. Oakhill
  • Article
    | Open Access

    A major drawback in the clinical use of the oral anticoagulants that directly inhibit factor Xa in order to prevent blood clot formation is the potential for life threatening bleeding events. Here the authors describe factor Xa variants that are refractory to inhibition by these anticoagulants and could serve as rescue agents in treated patients.

    • Daniël Verhoef
    • , Koen M. Visscher
    •  & Mettine H. A. Bos
  • Article
    | Open Access

    A growing number of ‘pseudoenzymes’ with a regulatory role in signal transduction processes but without catalytic activity are being identified. Here, the authors identify two pseudoGTPase domains in p190RhoGAP, characterize them biochemically and structurally and show that they influence RhoGAP activity.

    • Amy L. Stiegler
    •  & Titus J. Boggon
  • Article
    | Open Access

    Catalytic mechanisms of enzymes are well understood, but achieving diverse reaction chemistries in re-engineered proteins can be difficult. Here the authors show a highly efficient and thermostable artificial enzyme that catalyzes a diverse array of substrate oxidations coupled to the reduction of H2O2.

    • Daniel W. Watkins
    • , Jonathan M. X. Jenkins
    •  & J. L. Ross Anderson
  • Article
    | Open Access

    Active and inactive state ATP-phosphoribosyltransferases (ATP-PRTs) are believed to have different conformations. Here the authors show that in both states, ATP-PRT has a similar structural arrangement, suggesting that dynamic alterations are involved in ATP-PRT regulation by allosteric modulators.

    • João P. Pisco
    • , Cesira de Chiara
    •  & Luiz Pedro S. de Carvalho
  • Article
    | Open Access

    Some aerobic bacteria contain a biotin-independent malonate decarboxylase (MDC), which allows them to use malonate as the sole carbon source. Here, the authors present the crystal structure of a Pseudomonas MDC and give insights into its catalytic mechanism and function.

    • Riyaz Maderbocus
    • , Blanche L. Fields
    •  & Liang Tong
  • Article
    | Open Access

    The generation of glycolipid dolichylphosphate mannose (Dol-P-Man) is a critical step for protein glycosylation and GPI anchor synthesis. Here the authors report the structure of dolichylphosphate mannose synthase in complex with bound nucleotide and donor to provide insight into the mechanism of Dol-P-Man synthesis.

    • Rosaria Gandini
    • , Tom Reichenbach
    •  & Christina Divne
  • Article
    | Open Access

    γ-Glutamyltranspeptidases in gram-positive bacteria are not involved in glutathione metabolism, as their counterparts in eukaryotes and gram-negative bacteria. Here, the authors show that in Actinobacteria they catalyse the unusual cleavage of a C–C bond for the biosynthesis of non-proteinogenic amino acids.

    • Guannan Zhong
    • , Qunfei Zhao
    •  & Wen Liu
  • Article
    | Open Access

    The biosynthesis of xiamycin, an antimicrobial bacterial indolosesquiterpenoid, involves an unusual cyclization cascade. Here, the authors characterise the XiaF enzyme, which resembles xenobiont-degrading enzymes and is responsible for a hidden indole hydroxylation step that triggers the cyclization reaction.

    • Susann Kugel
    • , Martin Baunach
    •  & Christian Hertweck
  • Article
    | Open Access

    Terpenes are bioactive natural products derived from plants with several commercial applications. Here, the authors engineer a cell-free system composed of 27 enzymes that convert glucose into terpenes, highlighting the potential of synthetic biochemistry approaches for biocompounds production.

    • Tyler P. Korman
    • , Paul H. Opgenorth
    •  & James U. Bowie
  • Article
    | Open Access

    Arginine methylation is an abundant post-translational modification catalysed by protein arginine methyltransferases (PRMTs). Here the authors use quantitative mass spectrometry to globally profile the substrates of the PRMT CARM1 in breast cancer cells, and establish a role for CARM1’s N-terminus in substrate recognition.

    • Evgenia Shishkova
    • , Hao Zeng
    •  & Wei Xu
  • Article
    | Open Access

    Nonribosomal peptides are important bioactive molecules that are synthetized by enzymes containing several catalytic domains. Here the authors describe the catalytic mechanism of fungal nonribosomal peptide synthetases and present an approach to modify these enzymes to produce specific nonribosomal peptides.

    • Dayu Yu
    • , Fuchao Xu
    •  & Jixun Zhan
  • Article
    | Open Access

    Bacterial proteins are synthesized with formyl-methionine in their N-terminus, but most of them are co-translationally deformylated. Here, the authors show that inner-membrane proteins are protected from deformylation by the binding of the signal recognition particle (SRP) during translation.

    • Amitabh Ranjan
    • , Evan Mercier
    •  & Wolfgang Wintermeyer
  • Article
    | Open Access

    Polyamines bind to nucleic acids and their function is regulated by reversible acetylation. Here, the authors show that histone deacetylase 10 is a polyamine deacetylase and present its crystal structure with a bound polyamine transition state analogue inhibitor.

    • Yang Hai
    • , Stephen A. Shinsky
    •  & David W. Christianson
  • Article
    | Open Access

    A metabolon is a complex of sequential metabolic enzymes that channels substrates directly between enzymes, thus optimizing metabolic flux. Here Zhanget al. provide protein interaction and isotope dilution data that support the existence of a metabolon that channels both citrate and fumarate in the plant TCA cycle.

    • Youjun Zhang
    • , Katherine F. M. Beard
    •  & Toshihiro Obata
  • Article
    | Open Access

    Activity-based protein profiling (ABPP) is a chemical proteomics method to profile activity states of enzymes under physiological conditions. Here the authors show that ABPP can be applied to archaeal serine hydrolases in the model organismSulfolobus acidocaldariusand can be used to identify novel putative serine hydrolases.

    • Susanne Zweerink
    • , Verena Kallnik
    •  & Markus Kaiser
  • Article
    | Open Access

    Cytidine deaminases are evolutionarily conserved enzymes that edit genomes by deaminating cytidine to uridine. Here the authors present the crystal structure of APOBEC3A with a single-stranded DNA substrate bound in the active site to shed light on the mechanism and specificity of substrate recognition.

    • Takahide Kouno
    • , Tania V. Silvas
    •  & Celia A. Schiffer
  • Article
    | Open Access

    Glutaredoxins have important roles in redox processes. Here the authors show that the enzymatic activity of glutaredoxins requires two distinct glutathione interactions sites, one recognizing the glutathione disulfide substrate and one activating glutathione as a reducing agent.

    • Patricia Begas
    • , Linda Liedgens
    •  & Marcel Deponte
  • Article
    | Open Access

    USP9X is a deubiquitinating enzyme with many known substrates and functions; it has been linked to cancer but the mechanisms remain unclear. Here Liet al. report that USP9X stabilizes the centrosomal protein CEP131 leading to centrosome amplification and breast cancer development.

    • Xin Li
    • , Nan Song
    •  & Lei Shi
  • Article
    | Open Access

    The N-end rule pathway targets substrate proteins for proteasomal degradation. Here, Whiteet al. show that ArabidopsisPLANT CYSTEINE OXIDASEs show dioxygenase activity producing Cys-sulfinic acid at the N-terminus of target proteins, which then act as direct substrates for arginyl transferase.

    • Mark D. White
    • , Maria Klecker
    •  & Emily Flashman
  • Article
    | Open Access

    Although not photosynthetic, some archaea possess RuBisCO, one of the enzymes characteristic of the photosynthetic Calvin-Benson cycle, but apparently lack another one, phosphoribulokinase (PRK). Here the authors describe a carbon metabolic pathway in methanogenic archaea, involving RuBisCO and PRK.

    • Takunari Kono
    • , Sandhya Mehrotra
    •  & Hiroki Ashida
  • Article
    | Open Access

    DNA sliding clamps are ring-shaped proteins that encircle DNA and harbour polymerases and other factors that promote processive DNA replication. Here the authors use X-ray crystallography, NMR and MD simulations to propose a model for a PCNA sliding mechanism that relies on short-lived polar interactions.

    • Matteo De March
    • , Nekane Merino
    •  & Alfredo De Biasio
  • Article
    | Open Access

    ATP-binding cassette (ABC) transporters hydrolyse ATP to transport molecules across the cell membrane. Here Vogelet al. show that the ABC exporter MsBA can couple ATP hydrolyse to an adenylate kinase activity that seems to be predominant at low ATP levels and a general feature of ABC exporters.

    • Hundeep Kaur
    • , Andrea Lakatos-Karoly
    •  & Clemens Glaubitz
  • Article
    | Open Access

    Polyketides are typically assembled from a starter unit and malonyl- and/or methylmalonyl-CoA-derived extender units, but the macrolide antibiotics stambomycins incorporate non-standard alkylmalonyl-CoA extender units. Here, the authors describe the biosynthetic pathway responsible for this unusual synthesis.

    • Lauren Ray
    • , Timothy R. Valentic
    •  & Gregory L. Challis
  • Article
    | Open Access

    Antibiotic resistance is common in environmental bacteria, including those living in isolated caves. Here, Pawlowskiet al. study one of these bacterial strains, showing that it is resistant to most clinically used antibiotics through a remarkable variety of mechanisms, some of which are new to science.

    • Andrew C. Pawlowski
    • , Wenliang Wang
    •  & Gerard D. Wright