Enzymes articles within Nature

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  • Letter |

    The structure of human ATP-citrate lyase, in complex with a newly developed small-molecule inhibitor, shows extensive conformational changes that reveal an allosteric site for the inhibitor to bind and indirectly compete with the citrate substrate.

    • Jia Wei
    • , Silvana Leit
    •  & Liang Tong

  • Letter |

    OTULIN, which removes ubiquitin chains deposited by LUBAC, promotes LUBAC activity by preventing its auto-ubiquitination, thereby supporting normal mouse embryo development and preventing pro-inflammatory cell death in adult mice.

    • Klaus Heger
    • , Katherine E. Wickliffe
    •  & Vishva M. Dixit

  • Letter |

    By engineering entropy-tuning changes into distal sites of a bacterial adenylate kinase, an allosteric tuning mechanism based on protein dynamics is revealed.

    • Harry G. Saavedra
    • , James O. Wrabl
    •  & Vincent J. Hilser

  • Letter |

    Electron cryomicroscopy structures are provided for all core and supernumerary protein subunits of mammalian complex I, a 45-subunit enzyme that powers eukaryotic respiration.

    • Jiapeng Zhu
    • , Kutti R. Vinothkumar
    •  & Judy Hirst

  • Letter |

    The crystal structure of the MraY enzyme from Aquifex aeolicus in complex with the naturally occurring nucleoside inhibitor muraymycin D2 (MD2) reveals that MraY undergoes a large conformational rearrangement near the active site after the binding of MD2, leading to the generation of a nucleoside-binding pocket and a peptide-binding site.

    • Ben C. Chung
    • , Ellene H. Mashalidis
    •  & Seok-Yong Lee

  • Letter |

    An unprecedented mechanism of ubiquitination that is independent of E1 and E2 enzymes, instead relying on activation of ubiquitin by ADP-ribosylation, and which is mediated by members of the SidE effector family encoded by the bacterial pathogen Legionella pneumophila, establishes that ubiquitination can be carried out by a single enzyme.

    • Jiazhang Qiu
    • , Michael J. Sheedlo
    •  & Zhao-Qing Luo

  • Article |

    This study describes a new model of eukaryotic replication termination in which converging leading strands pass each other unhindered and the replicative DNA helicase is unloaded late, after all strands have been ligated.

    • James M. Dewar
    • , Magda Budzowska
    •  & Johannes C. Walter

  • Letter |

    The crystal structure of mouse SCD1 bound to fatty acid stearoyl-CoA is solved at 2.6 Å resolution; the structure reveals a novel geometry for the dimetal centre, and the acyl chain of the bound fatty acid is shown to be shielded and shaped to a particular conformation by the enzyme, providing a structural basis for the selectivity of fatty acid metabolism.

    • Yonghong Bai
    • , Jason G. McCoy
    •  & Ming Zhou

  • Letter |

    Time-resolved resonance Raman vibrational spectroscopy was used to study the mechanism of soluble methane monooxygenase and obtain structural information on the key reaction cycle intermediate, compound Q, which contains a unique dinuclear FeIV cluster that breaks the strong C-H bond of methane and inserts an oxygen atom (from O2) to form methanol.

    • Rahul Banerjee
    • , Yegor Proshlyakov
    •  & Denis A. Proshlyakov

  • Letter |

    Four different XNAs — polymers with backbone chemistries not found in nature, namely, arabino nucleic acids, 2′-fluoroarabino nucleic acids, hexitol nucleic acids and cyclohexene nucleic acids — are found to be able to support the evolution of synthetic enzymes (XNAzymes) that catalyse several chemical reactions.

    • Alexander I. Taylor
    • , Vitor B. Pinheiro
    •  & Philipp Holliger

  • Letter |

    Here, a cross-chiral RNA polymerase is developed—an RNA enzyme that can catalyse the templated polymerization of activated mononucleotides that are of the opposite handedness—shedding light on how RNA-based life could have emerged.

    • Jonathan T. Sczepanski
    •  & Gerald F. Joyce

  • Article |

    The COP9 signalosome (CSN) complex regulates cullin–RING E3 ubiquitin ligases—the largest class of ubiquitin ligase enzymes, which are involved in a multitude of regulatory processes; here, the crystal structure of the entire human CSN holoenzyme is presented.

    • Gondichatnahalli M. Lingaraju
    • , Richard D. Bunker
    •  & Nicolas H. Thomä

  • Article |

    The three-dimensional structure of intact human γ-secretase complex at 4.5 Å resolution is revealed by cryo-electron-microscopy single-particle analysis; the complex comprises a horseshoe-shaped transmembrane domain containing 19 transmembrane segments, and a large extracellular domain from nicastrin, which sits immediately above the hollow space formed by the horseshoe.

    • Peilong Lu
    • , Xiao-chen Bai
    •  & Yigong Shi

  • Letter |

    Distinct groups of microorganisms have been thought to grow on methane and on short-chain alkanes; now, the methanotroph Methylocella silvestris is shown to express two distinct soluble di-iron centre monooxygenases that allow it to use either methane or propane as a carbon and energy source.

    • Andrew T. Crombie
    •  & J. Colin Murrell

  • Letter |

    A mechanism is proposed for the formation of methane by bacteria, through the cleavage of a highly unreactive carbon–phosphorus bond in methyl phosphonate by PhnJ in the bacterial C–P lyase complex.

    • Siddhesh S. Kamat
    • , Howard J. Williams
    •  & Frank M. Raushel

  • Letter |

    The sirtuin family of enzymes are known as NAD-dependent deacetylases, although some of them have very weak deacetylase activity; here human SIRT6, an enzyme important for DNA repair and transcription, is shown to remove long-chain fatty acyl groups from protein lysine residues, and to have a function in promoting tumour necrosis factor alpha secretion.

    • Hong Jiang
    • , Saba Khan
    •  & Hening Lin

  • Article |

    The atomic-resolution structure of the entire respiratory complex I is reported, with the resolution high enough to map out the locations and orientations of nearly all amino-acid side chains—some of which link to human neurodegenerative diseases—and reveals which amino-acid interactions take place at the hydrophilic domain–membrane domain interface.

    • Rozbeh Baradaran
    • , John M. Berrisford
    •  & Leonid A. Sazanov

  • Letter |

    The crystal structure of the complex between the hydroxylase and regulatory component of soluble methane monooxygenase is presented, revealing how the latter component controls substrate access to the hydroxylase active site.

    • Seung Jae Lee
    • , Michael S. McCormick
    •  & Uhn-Soo Cho

  • News & Views |

    Eyewitnesses are sometimes asked to identify a culprit from a line-up of people associated with a crime scene. An enzyme — iridoid synthase — that catalyses an unusual reaction has been identified by a similar approach. See Letter p.138

    • Joe Chappell

  • Letter |

    Iridoids are a large family of bicyclic natural products that possess anticancer, anti-inflammatory, antifungal and antibacterial activities; here the essential cyclization step in their biosynthesis is identified, opening up the possibility of production of naturally occurring and synthetic variants of iridoids for use in pharmacy or agriculture.

    • Fernando Geu-Flores
    • , Nathaniel H. Sherden
    •  & Sarah E. O’Connor

  • News & Views |

    Single-molecule studies reveal how the DNA-repair protein RecA overcomes competition from another protein to bind to single-stranded DNA, and how other mediator proteins assist in this process. See Letter p.274

    • Susan T. Lovett

  • News & Views |

    By freezing a DNA polymerase enzyme at several points along its reaction pathway, a sequence of X-ray crystal structures has been obtained, showing how the enzyme replicates DNA and revealing surprising mechanistic details. See Article p.196

    • Kenneth A. Johnson

  • Article |

    The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis; using in vivo RNA interference and mathematical modelling it is shown here that the endolysosomal system is resilient to loss of Rab5 until its concentration drops below a critical level, at which point endosomes are lost, leading to increased serum low-density lipoprotein levels, alterations in metabolism and hepatocellular polarity.

    • Anja Zeigerer
    • , Jerome Gilleron
    •  & Marino Zerial

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