Enzymes articles within Nature Communications

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  • Article
    | Open Access

    The mammalian retina is a modular brain region, in which cell layers are of uniform thickness but the molecular mechanism controlling this process is not well understood. Here the authors identify a regulatory network consisting of the long noncoding RNA Rncr4, RNA helicase Ddx3x and miR-183/96/182 that controls the even distribution of cells across layers.

    • Jacek Krol
    • , Ilona Krol
    •  & Witold Filipowicz

  • Article
    | Open Access

    Lipid droplets (LDs) supply fatty acids to cellular processes and move bidirectionally on microtubules. Here the authors show that nutrient starvation causes dispersal of mitochondria and LD to the periphery of the cell along detyrosinated microtubules and increases LD–mitochondria interactions in an AMPK-dependent manner.

    • Albert Herms
    • , Marta Bosch
    •  & Albert Pol

  • Article
    | Open Access

    Polypeptide GalNAc-transferases decorate proteins with dense arrays of O-glycans, which in the case of mucins are essential for their barrier functions. Here the authors present comprehensive structural studies that shed light on the molecular attributes that allow GalNAc-T2 to efficiently carry out dense O-glycosylation.

    • Erandi Lira-Navarrete
    • , Matilde de las Rivas
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    Fluoroquinolone antibiotics are widely used to treat serious bacterial infections, but resistance is an increasing problem. Here the authors describe the synthesis and characterization of novel deoxynybomycin derivatives that exhibit activity against fluoroquinolone-resistant infections in an in vivomodel.

    • Elizabeth I. Parkinson
    • , Joseph S. Bair
    •  & Paul J. Hergenrother

  • Article |

    Mammalian female meiosis is error prone, with error rates increasing with age. Here Touati et al. show that the spindle assembly checkpoint (SAC) protein BubR1, which decreases with age, has multiple roles in meiosis I by controlling SAC, stabilizing the mitotic spindle and timing the onset of anaphase I.

    • Sandra A. Touati
    • , Eulalie Buffin
    •  & Katja Wassmann

  • Article |

    Elastase secreted by immune cells contributes to various lung diseases; however, elastase inhibitors have mostly failed in the clinic. Here, the authors discover a second, truncated form of elastase, which is the result of autocatalytic cleavage and is not well targeted by current synthetic elastase inhibitors.

    • T. Dau
    • , R. S. J. Sarker
    •  & D. E. Jenne

  • Article
    | Open Access

    Arginine methylation is an important regulatory post-translational modification. Here, the authors present a new SILAC-based method—iMethyl-SILAC—that allows unambiguous identification of arginine-methylated peptide pairs by mass spectrometry and apply it to greatly expand the known T-cell arginine methylome.

    • Vincent Geoghegan
    • , Ailan Guo
    •  & Oreste Acuto

  • Article |

    Protein arginine methylation is an abundant post-translational modification often associated with RNA-binding proteins. Here the authors show that the previously uncharacterized PRMT9 enzyme catalyses the symmetrical methylation of SAP145, which promotes its association with the SMN complex and regulates splicing.

    • Yanzhong Yang
    • , Andrea Hadjikyriacou
    •  & Mark T. Bedford

  • Article |

    Enzymatic catalytic processes have great industrial potential, although their application is hampered by stability and reuse issues. Here, the authors report metal-organic frameworks with rationally designed single-molecule traps for enzyme encapsulation, and evaluate the activity of the confined enzymes.

    • Dawei Feng
    • , Tian-Fu Liu
    •  & Hong-Cai Zhou

  • Article |

    It is known that some nanomaterials can exhibit enzyme-like activities, prompting interest in the novel applications this property may allow. Here, the authors show how vanadia nanowires possess glutathione peroxidase-like activity, and can effectively protect cells from oxidative damage.

    • Amit A. Vernekar
    • , Devanjan Sinha
    •  & Govindasamy Mugesh

  • Article |

    Inositol trisphosphate kinases (IP3Ks) and inositol hexakisphosphate kinases (IP6Ks) are involved in signalling by phosphorylating their specific targets. Here, Wang et al.report the crystal structure of a hybrid IP6K/IP3K enzyme, analyse the substrate orientations and propose an evolutionary trajectory for this kinase family.

    • Huanchen Wang
    • , Eugene F. DeRose
    •  & Stephen B. Shears

  • Article
    | Open Access

    Penicillin inhibits growth of chlamydial pathogens despite their lack of a conventional peptidoglycan cell wall. Here the authors report that the chlamydial amidase, AmiA, which can rescue cell division defects of an E. coli amiAmutant, has dual activity as a penicillin sensitive, lipid II-targetting carboxypeptidase.

    • Anna Klöckner
    • , Christian Otten
    •  & Beate Henrichfreise

  • Article |

    The transfer of a phosphate group from a CDP-linked donor to an acceptor alcohol is catalysed by CDP-alcohol phosphotransferases. Here, Sciara et al. report crystal structures of a CDP-alcohol phosphotransferase, define roles of conserved residues and propose a mechanism of action for this protein family.

    • Giuliano Sciara
    • , Oliver B. Clarke
    •  & Filippo Mancia

  • Article
    | Open Access

    Type II PI4-kinase dysfunction is associated with diseases including cancer and Alzheimer's disease; however, the development of specific modulators has been hampered by a lack of structural information. Zhou et al. present the crystal structure of PI4KIIα in its ADP-bound form, providing insight into its regulation.

    • Qiangjun Zhou
    • , Jiangmei Li
    •  & Chang Chen

  • Article
    | Open Access

    Cyclin-dependent kinase 12 (Cdk12) phosphorylates the C-terminal domain (CTD) of RNA polymerase II to regulate transcription. Here, the authors solve the crystal structure of the Cdk12 kinase domain and show that Cdk12 has its highest activity on a CTD substrate that carries a serine 7 phosphorylation.

    • Christian A. Bösken
    • , Lucas Farnung
    •  & Matthias Geyer

  • Article |

    The phosphorylation of proteins is a common mechanism for signal transduction. Here, the authors present a structural analysis of a histidine kinase in the process of autophosphorylation, helping to elucidate the catalytic mechanism.

    • Patricia Casino
    • , Laura Miguel-Romero
    •  & Alberto Marina

  • Article |

    Spitzoid neoplasms constitute a spectrum of melanocytic tumours, characterized by distinct clinical, pathological and genetic features. Here, Wiesner et al. show that kinase fusions represent the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanoma.

    • Thomas Wiesner
    • , Jie He
    •  & Boris C. Bastian

  • Article
    | Open Access

    Topoisomerases facilitate the progress of elongating polymerases during transcription. Zomerdijk and colleagues now demonstrate an additional role for this enzyme; their data suggest that Top2 can cleave DNA inducing topological changes at the ribosomal DNA promoter, which assists de novoassembly of the RNA polymerase I pre-initiation complex.

    • Swagat Ray
    • , Tatiana Panova
    •  & Joost C. B. M. Zomerdijk

  • Article
    | Open Access

    Phosphoenolpyruvate carboxylase, the key enzyme of C4 photosynthesis, evolved from an ancestral isoform in C3 plants and has a reduced feedback inhibition. Paulus et al.show that enhanced inhibitor tolerance of C4 phosphoenolpyruvate carboxylase is achieved by a single amino-acid exchange.

    • Judith Katharina Paulus
    • , Daniel Schlieper
    •  & Georg Groth

  • Article
    | Open Access

    The mitochondrial protease CLPP is found in most eukaryotic organisms but its biological role has been unclear. Here Osiewacz and colleagues show that deletion of CLPP extends lifespan of the filamentous fungus Podospora anserina, and that human and fungal CLPP are functionally conserved.

    • Fabian Fischer
    • , Andrea Weil
    •  & Heinz D. Osiewacz

  • Article
    | Open Access

    Despite the central importance of NADP+ in mitochondrial energy metabolism, no NAD kinase has been found in human mitochondria to synthesize NADP+. These authors show C5orf33, a protein specific to animals and protists, to be the missing NAD kinase and demonstrate its mitochondrial localization and activity.

    • Kazuto Ohashi
    • , Shigeyuki Kawai
    •  & Kousaku Murata

  • Article |

    Enzymes are traditionally viewed as being highly specific for their substrates. Tokuriki et al.follow the accumulation of mutations during the laboratory evolution of a phosphotriesterase into an arylesterase, and postulate that many naturally occurring enzymes may not be optimal for their substrates.

    • Nobuhiko Tokuriki
    • , Colin J. Jackson
    •  & Dan S. Tawfik

  • Article |

    Sequence-specific DNA endonucleases have found numerous applications in biology, but similar manipulations of RNA have been limited by the lack of suitable enzymes. These authors combine a cleavage domain with a designable binding domain and demonstrate the resulting RNA endonuclease's utilityin vitroand in cells.

    • Rajarshi Choudhury
    • , Yihsuan S. Tsai
    •  & Zefeng Wang

  • Article |

    Methyltransferases modify cellular proteins in addition to DNA and histones. These authors identify a new family of lysine-specific methyltransferases and show that a member of this family, which is associated with tumour metastasis, methylates the ATP-dependent protein chaperone VCP/p97.

    • Stefan Kernstock
    • , Erna Davydova
    •  & Pål Ø. Falnes

  • Article
    | Open Access

    G-protein-coupled receptors sense extracellular cues and transmit the signal to distinct trimeric G-proteins. Stefanet al.show that in response to cAMP, a central and conserved component of the Gαs-coupled receptor cascade, the RII subunit of PKA, specifically binds to and participates in Gαi signaling.

    • Eduard Stefan
    • , Mohan K. Malleshaiah
    •  & Stephen W. Michnick

  • Article |

    Large scale synapse assays can facilitate identification of drug leads. Shiet al. develop a 'synapse microarray' technology that enables sensitive, high-throughput, quantitative screening of synaptogenic events, and use it to identify novel histone deacetylase inhibitors that enhance synaptogenesis.

    • Peng Shi
    • , Mark A. Scott
    •  & Mehmet Fatih Yanik

  • Article |

    Thioredoxin reductase 1 is a flavoprotein that is involved in the regulation of redox homeostasis. Fritz-Wolfet al. report the first crystal structures of thioredoxin reductase 1 in complex with its substrate, thioredoxin, and confirm that the enzyme uses a flexible carboxy-terminal arm for electron transport to its substrates.

    • Karin Fritz-Wolf
    • , Sebastian Kehr
    •  & Katja Becker

  • Article
    | Open Access

    ADAR enzymes edit double-stranded RNA, converting adenosines to inosines, and are essential for neuronal function. Eggingtonet al. quantify edit sites in RNA using a Sanger sequencing protocol and use the resulting data to develop algorithms to predict RNA edit sites.

    • Julie M. Eggington
    • , Tom Greene
    •  & Brenda L. Bass

  • Article
    | Open Access

    The Q-cycle is thought to be an essential energetic component of the photosynthetic electron-transfer chain. Here, Chlamydomonas mutants with an inactive Q-cycle but normal levels ofb6fcomplexes are shown to display photosynthetic growth, demonstrating the dispensability of the Q-cycle in the oxygenic photosynthetic chain.

    • Alizée Malnoë
    • , Francis-André Wollman
    •  & Fabrice Rappaport

  • Article |

    Little is known about the effects of molecular crowding and confinement on biomolecule function. Castronovoet al. investigate the reactions of restriction enzymes with DNA confined in bushy matrices and find that the enzymes enter at the side of the matrix before diffusing two-dimensionally.

    • Matteo Castronovo
    • , Agnese Lucesoli
    •  & Giacinto Scoles

  • Article |

    Uridines at the wobble position of transfer RNA anticodons are usually modified to allow efficient decoding of messenger RNA codons. In this study, ALKBH8 is shown to be a bifunctional transfer RNA modification enzyme required for the formation of a novel diastereomeric pair of modified wobble uridines.

    • Erwin van den Born
    • , Cathrine B. Vågbø
    •  & Pål Ø. Falnes

  • Article |

    Macroautophagy involves remodelling of intracellular membranes, but the role of lipids and lipid enzymes in this process is poorly understood. Here, the authors demonstrate that phospholipase D1, an enzyme that catalyses the production of phosphatidic acid, has a modulatory role in the autophagy process in mammalian cells.

    • Claudia Dall'Armi
    • , Andrés Hurtado-Lorenzo
    •  & Gilbert Di Paolo

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