Enzyme mechanisms articles within Nature

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  • Article
    | Open Access

    Binding of the substrates NAD+ and ATP to the plant Toll/interleukin-1 receptor (TIR) domain proteins induces phase separation and, thereby, activation of TIR enzymatic and immune signalling activity.

    • Wen Song
    • , Li Liu
    •  & Jijie Chai

  • Article
    | Open Access

    The Bacteroides fragilis type III CRISPR protein Cmr conjugates ATP to S-adenosyl methionine, generating S-adenosyl methionine (SAM)-AMP, a novel second messenger with a role in antiviral signalling.

    • Haotian Chi
    • , Ville Hoikkala
    •  & Malcolm F. White

  • Article
    | Open Access

    X-ray, cryo-EM and kinetic studies of the circadian oscillator KaiBC from the photosynthetic bacterium Rhodobacter sphaeroides shed light on the evolution of self-regulating oscillators.

    • Warintra Pitsawong
    • , Ricardo A. P. Pádua
    •  & Dorothee Kern

  • Article
    | Open Access

    Structural and biochemical studies of the Mycobacterium smegmatis hydrogenase Huc provides insights into how [NiFe] hydrogenases oxidize trace amounts of atmospheric hydrogen and transfer the electrons liberated via quinone transport.

    • Rhys Grinter
    • , Ashleigh Kropp
    •  & Chris Greening

  • Article |

    Cryo-EM is used to visualize the SARS-CoV-2 RTC bound to each of the natural NTPs as well as remdesivir triphosphate (RDV-TP) in states poised for incorporation, explaining the interactions required for NTP recognition and RDV-TP selectivity.

    • Brandon F. Malone
    • , Jason K. Perry
    •  & Seth A. Darst

  • Article
    | Open Access

    Cryo-electron microscopy structures of Staphylococcus aureus BlaR1 reveal dynamic signalling states regulating broad spectrum β-lactam antibiotic resistance through cleavage of the transcriptional repressor BlaI and induced expression of the β-lactamase blaZ and the β-lactam-resistant cell-wall transpeptidase mecA.

    • J. Andrew N. Alexander
    • , Liam J. Worrall
    •  & Natalie C. J. Strynadka

  • Article
    | Open Access

    Structural analysis of Cas12a2, a CRISPR-associated nuclease that nonspecifically cleaves ssRNA, ssDNA and dsDNA, reveals a complete activation pathway involved in the abortive infection system protecting cells against invasion.

    • Jack P. K. Bravo
    • , Thomson Hallmark
    •  & David W. Taylor

  • Article
    | Open Access

    The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.

    • Seiichi Hirano
    • , Kalli Kappel
    •  & Feng Zhang

  • Article |

    Cryo-electron microscopy studies of Escherichia coli complex I suggest a conserved mechanism of coupled proton transfers and electrostatic interactions that result in proton ejection from the complex exclusively at the distal NuoL subunit.

    • Vladyslav Kravchuk
    • , Olga Petrova
    •  & Leonid Sazanov

  • Article
    | Open Access

    Reconstitution of the SARS-CoV-2 RNA 5′ cap reveals the unconventional mechanism by which SARS-CoV-2 caps its RNA genome, providing a new target in the development of antiviral agents to treat COVID-19.

    • Gina J. Park
    • , Adam Osinski
    •  & Vincent S. Tagliabracci

  • Article
    | Open Access

    Biochemical and lipidomic analyses identify an anti-ferroptotic function of vitamin K and reveal ferroptosis suppressor protein 1 (FSP1) as the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle.

    • Eikan Mishima
    • , Junya Ito
    •  & Marcus Conrad

  • Article
    | Open Access

    A structure of the MRAS–SHOC2–PP1C complex supports a RAS-driven and multi-molecular model for RAF activation in which individual RAS–GTP molecules recruit RAF–14-3-3 and SHOC2–PP1C to activate the downstream pathway.

    • Zachary J. Hauseman
    • , Michelle Fodor
    •  & Daniel A. King

  • Article
    | Open Access

    Chimeric triterpene synthases are identified that catalyse non-squalene-dependent triterpene biosynthesis.

    • Hui Tao
    • , Lukas Lauterbach
    •  & Tiangang Liu

  • Article
    | Open Access

    Cryo-electron microscopy structures of Cas9 during mismatch cleavage provide insight into the mechanisms that control off-target effects of Cas9, which will aid in the future design of high-fidelity Cas9 variants with reduced off-target cleavage.

    • Jack P. K. Bravo
    • , Mu-Sen Liu
    •  & David W. Taylor

  • Article |

    Combining NMR spectroscopy-derived pseudocontact shifts (PCSs) with Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion enables protein structure determination of lowly populated high-energy states that are essential for macromolecular function.

    • John B. Stiller
    • , Renee Otten
    •  & Dorothee Kern

  • Article
    | Open Access

    Structural and spectroscopic studies show how a B12-dependent radical SAM enzyme catalyses unique and challenging alkylation chemistry, including protein post-translational modification required for methane biosynthesis.

    • Cameron D. Fyfe
    • , Noelia Bernardo-García
    •  & Olivier Berteau

  • Article |

    Unphosphorylated PINK1 of Pediculus humanus corporis forms a dimerized state before undergoing trans-autophosphorylation, and phosphorylated PINK1 undergoes a conformational change in the N-lobe to produce its phosphorylated, ubiquitin-binding state.

    • Zhong Yan Gan
    • , Sylvie Callegari
    •  & David Komander

  • Article |

    Bacteria in the human gut and oral microbiome encode enzymes that selectively phosphorylate the antidiabetic drug acarbose—an inhibitor of both human and bacterial α-glucosidases—resulting in its inactivation and limiting the drug's effects on the ability of the host to metabolize complex carbohydrates.

    • Jared Balaich
    • , Michael Estrella
    •  & Mohamed S. Donia

  • Article |

    Structures of Ubr1 in complex with Ubc2, ubiquitin and two N-degron peptides reveal a Ubc2-binding region and an acceptor ubiquitin-binding loop on Ubr1, providing mechanistic insights into the initiation and elongation steps of ubiquitination catalysed by Ubr1.

    • Man Pan
    • , Qingyun Zheng
    •  & Minglei Zhao

  • Article |

    A small proportion of Spo11-dependent DNA double-strand breaks are ‘double cuts’—adjacent breaks that occur in concert—revealing that gap repair during meiosis includes that of DNA gaps generated by Spo11 itself.

    • Dominic Johnson
    • , Margaret Crawford
    •  & Matthew J. Neale

  • Article |

    A NOS bridge between cysteine and lysine residues serves as an allosteric redox switch in the transaldolase enzyme of Neisseria gonorrhoeae, demonstrating the existence of protein regulatory switches that contain covalent crosslinks other than disulfides.

    • Marie Wensien
    • , Fabian Rabe von Pappenheim
    •  & Kai Tittmann

  • Article |

    A high-resolution structure of human telomerase bound to telomeric DNA reveals details of telomerase assembly and its active site, and sheds light on how mutations alter telomerase function.

    • George E. Ghanim
    • , Adam J. Fountain
    •  & Thi Hoang Duong Nguyen

  • Article |

    Serial synchrotron crystallography reveals the structure of the human glycine transporter GlyT1, showing how a state-specific inhibitor exerts its effects, and potentially informing the design of new GlyT1 inhibitors to treat a range of disorders of the central nervous system.

    • Azadeh Shahsavar
    • , Peter Stohler
    •  & Poul Nissen

  • Article |

    The molecular steps that lead to the disaggregation of amyloid fibrils are shown to involve the synergistic action of HSP70 and its co-chaperones DNAJB1 and HSP110.

    • Anne S. Wentink
    • , Nadinath B. Nillegoda
    •  & Bernd Bukau

  • Article |

    Cryo-electron microscopy structures of the bacterial recombination protein RecA with DNA, and of RecA–D-loop complexes, provide insights into the double-stranded DNA opening, homology search and strand-exchange processes of homologous recombination.

    • Haijuan Yang
    • , Chun Zhou
    •  & Nikola P. Pavletich

  • Article |

    Analysis of two homologous groups of fungal pericyclases demonstrates how they can catalyse either an Alder-ene reaction—which has not previously been found in nature—or a hetero-Diels–Alder reaction.

    • Masao Ohashi
    • , Cooper S. Jamieson
    •  & Yi Tang

  • Article |

    Structural studies of the dimerization quality control E3 ubiquitin ligase SCF–FBXL17 indicate that its selectivity for aberrant complex formation is based on recognizing both shape and complementarity of interacting domains.

    • Elijah L. Mena
    • , Predrag Jevtić
    •  & Michael Rape

  • Article |

    The yeast E3 ligase Bre1 forms a core–shell condensate with the scaffold protein Lge1, implicating liquid–liquid phase separation as a mechanism in the ubiquitination of histone H2B along gene bodies.

    • Laura D. Gallego
    • , Maren Schneider
    •  & Alwin Köhler

  • Article |

    The cryo-electron microscopy structure of human thyroglobulin reveals that proximity, flexibility and solvent exposure are key characteristics of its hormonogenic tyrosine pairs, and provides a framework for understanding the formation of thyroid hormones.

    • Francesca Coscia
    • , Ajda Taler-Verčič
    •  & Jan Löwe

  • Article |

    Analysis of multiple structures of the Helicoverpa zea DNA transposase Transib, determined by X-ray crystallography and cryo-electron microscopy, reveals the detailed pathway of the transposition reaction and sheds light on the evolution of the RAG recombinase.

    • Chang Liu
    • , Yang Yang
    •  & David G. Schatz

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