Enzyme mechanisms articles within Nature Communications

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  • Article
    | Open Access

    UBA6 is an E1 enzyme that can activate both ubiquitin and FAT10. Here, the authors employ X-ray crystallography and biochemical techniques to explain this dual specificity, and identify UBA6 variants that are selectively impaired in the activation of either ubiquitin or FAT10.

    • Ngoc Truongvan
    • , Shurong Li
    •  & Hermann Schindelin

  • Article
    | Open Access

    Iridoid compounds are an important class of natural products. Here, the authors report on the discovery and engineering of nepetalactol-related short chain reductases and their application for the biosynthesis of nepetalactol or nepetalactone stereoisomers, as a versatile system for the production of the iridoid natural product scaffold.

    • Néstor J. Hernández Lozada
    • , Benke Hong
    •  & Sarah E. O’Connor

  • Article
    | Open Access

    Deubiquitinases (DUBs) targeting Met1-linked ubiquitin chains have important functions in mammals but are barely studied in plants. Here, the authors identify rice OTUB1 as a Met1-targeting DUB, characterize the structural determinants of this activity, and show that these features are conserved in green plants.

    • Lining Lu
    • , Xiaoguo Zhai
    •  & Feng Wang

  • Article
    | Open Access

    Release of the ATP hydrolysis product orthophosphate (Pi) from the myosin active site is central in force generation but is poorly understood. Here, Moretto et al. present evidence for multistep Pi-release reconciling apparently contradictory results.

    • Luisa Moretto
    • , Marko Ušaj
    •  & Alf Månsson

  • Article
    | Open Access

    Synthesis of lipopolysaccharides, essential components for most gram-negative bacteria, is under tight control. Here, authors use in vitro reconstitution and structural approaches to elucidate some of these regulatory mechanisms involving essential membrane proteins LapB and YejM.

    • Sheng Shu
    •  & Wei Mi

  • Article
    | Open Access

    Macrocyclization is an important process in bioactive natural product synthesis. Here, the authors report on the study of a macrocyclic ring constructing enzyme in the biosynthesis of alchivemycin A and using gene deletion, biochemical assays and isotope labelling show the enzyme catalyses tandem dehydration and Michael-type addition.

    • Hong Jie Zhu
    • , Bo Zhang
    •  & Hui Ming Ge

  • Article
    | Open Access

    AM0627 is a bis-O-glycan mucinase that might work in the final steps of mucus degradation, thereby providing a carbon and nitrogen source for Akkermansia muciniphila. Here, the authors provide molecular insights into AM0627 function from X-ray crystallography and computer simulations.

    • Víctor Taleb
    • , Qinghua Liao
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    Entomopathogenic bacteria used for pest control secrete potent Tc toxins. Here, the authors combine biochemistry, solution and solid-state NMR spectroscopy and cryo-EM to show in atomic detail how the toxin disrupts the host cell cytoskeleton and kills the target cell.

    • Alexander Belyy
    • , Florian Lindemann
    •  & Stefan Raunser

  • Article
    | Open Access

    Glycogen is a major energy reserve in eukaryotes and is synthesised in part by glycogenin (GN) and glycogen synthase (GS). Here, authors describe the structural basis of GS regulation, specifically the mechanism of inactivation by phosphorylation.

    • Laura Marr
    • , Dipsikha Biswas
    •  & Elton Zeqiraj

  • Article
    | Open Access

    DNA polymerase (pol) λ performs DNA synthesis in base excision and double strand break repair. How pol λ accomplishes nucleotide insertion that can lead to mutagenesis and genomic instability was unclear. Here the authors employ time-lapse crystallography to reveal hidden polymerase checkpoints that enable right and wrong natural nucleotide insertion by pol λ.

    • Joonas A. Jamsen
    • , David D. Shock
    •  & Samuel H. Wilson

  • Article
    | Open Access

    Catharanthus roseus is the source for anticancer drug vinblastine and other medicinal monoterpenoid indole alkaloids. Here the authors characterize an Fe/2OG dioxygenase, vindolinine synthase, which catalyzes an unusual redox-neutral reaction leading to alkaloid diversity.

    • Jasmine Ga May Eng
    • , Mohammadamin Shahsavarani
    •  & Yang Qu

  • Article
    | Open Access

    DNA N6-adenine methylation (6 mA) plays a crucial role in epigenetic regulation in eukaryotes. Here, the authors determined nine crystal structures of the ciliates 6 mA methyltransferase complexes, providing the molecular basis for understanding the functions of 6 mA.

    • Jiyun Chen
    • , Rong Hu
    •  & Liang Liu

  • Article
    | Open Access

    DISARM (Defense Island System Associated with Restriction Modification) systems can provide bacteria with protection against a wide range of phage. Here, Bravo et al. determine cryo-EM structures of the core DISARM complex that shed light onto phage DNA recognition and activation of this widespread defense system.

    • Jack P. K. Bravo
    • , Cristian Aparicio-Maldonado
    •  & David W. Taylor

  • Article
    | Open Access

    S-methyl methionine (SMM) is a key molecule in production of dimethylsulfoniopropionate (DMSP), an important marine anti-stress compound, with roles in global nutrient cycling. Here, the authors determine the mechanism of SMM synthesis and uncover unexpected roles for SMM in archaea, CPR bacteria and animals.

    • Ming Peng
    • , Chun-Yang Li
    •  & Yu-Zhong Zhang

  • Article
    | Open Access

    Using cryo-EM, Chung et al. investigate conformational states of mammalian respiratory complex I to reveal an ubiquinone-10 molecule occupying the full length of the Q-binding channel. Molecular dynamics simulations suggest how the charge states of key residues influence the substrate binding pose.

    • Injae Chung
    • , John J. Wright
    •  & Judy Hirst

  • Article
    | Open Access

    The p97 unfoldase is an essential and abundant enzyme that segregates its substrates from macromolecular complexes and organelle membranes. Here, authors determined the structure of human p97 in the act of unfolding an authentic substrate.

    • Yang Xu
    • , Han Han
    •  & Peter S. Shen

  • Article
    | Open Access

    Pericyclase enzymes are an expanding family of enzymes. Here, the authors identify the norbornene synthase SdnG, a pericyclase for the intramolecular Diels-Alder reaction between a cyclopentadiene and an olefinic dienophile to form the sordaricin norbornene structure, and reconstitute the sordaricin biosynthesis.

    • Zuodong Sun
    • , Cooper S. Jamieson
    •  & Yi Tang

  • Article
    | Open Access

    Statin therapy is associated with numerous cellular effects. Here, the authors show that statin treatment increases post-translational modifications on fatty acid synthase in the active site, revealing communication between the cholesterol and lipid biosynthetic pathways.

    • Alec G. Trub
    • , Gregory R. Wagner
    •  & Matthew D. Hirschey

  • Article
    | Open Access

    The glycosyltransferase C1GalT1 directs a key step in protein O-glycosylation important for the expression of the cancer-associated Tn and T antigens. Here, the authors provide molecular insights into the function of C1GalT1 by solving the crystal structure of the Drosophila enzyme-substrate complex.

    • Andrés Manuel González-Ramírez
    • , Ana Sofia Grosso
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    MicroRNA precursors are cleaved by DICER to generate mature microRNAs in the cytoplasm. Here the authors employ high-throughput analysis of DICER cleavage activity and identify RNA secondary elements in precursor miRNAs and shRNAs, including a single nucleotide bulge, which govern its cleavage efficiency and accuracy.

    • Trung Duc Nguyen
    • , Tam Anh Trinh
    •  & Tuan Anh Nguyen

  • Article
    | Open Access

    Presequence protease (PreP) is essential to mitochondrial proteostasis. This study leverages advanced vitrification techniques to solve cryoEM structures of apo- and substrate-bound PreP and integrates these data with other analysis to reveal key stages and mechanistic insights of the PreP catalytic cycle.

    • Wenguang G. Liang
    • , Juwina Wijaya
    •  & Wei-Jen Tang

  • Article
    | Open Access

    RecBCD is a remarkably fast DNA helicase. Using a battery of biophysical methods, Zananiri et. al reveal additional, non-catalytic ATP binding sites that increase the ATP flux to the catalytic sites that allows fast unwinding when ATP is scarce.

    • Rani Zananiri
    • , Sivasubramanyan Mangapuram Venkata
    •  & Arnon Henn

  • Article
    | Open Access

    “Mapping the dark matter of metabolism remains an open challenge that can be addressed globally and systematically by existing computational solutions. Here the authors present ATLASx, a repository of known and predicted enzymatic reaction, connecting millions of compounds to help synthetic biologists and metabolic engineers to design and explore metabolic pathways.”

    • Homa MohammadiPeyhani
    • , Jasmin Hafner
    •  & Vassily Hatzimanikatis

  • Article
    | Open Access

    Pausing of RNA polymerase (RNAP) and transcription is regulated by the NusA and NusG transcription factors in bacteria. Here the authors provide structural evidence for how they interact with RNAP to carry out their pausing roles and also reveal functions for NusA and NusG in transcription termination.

    • Chengjin Zhu
    • , Xieyang Guo
    •  & Albert Weixlbaumer

  • Article
    | Open Access

    The Dbf4-dependent kinase Cdc7 (DDK) is essential for eukaryotic DNA replication. Here, the authors present a series of cryo-EM structures elucidating the versatility of this kinase in exerting an ordered phosphorylation of its essential target to promote replication initiation.

    • Jiaxuan Cheng
    • , Ningning Li
    •  & Yuanliang Zhai

  • Article
    | Open Access

    Cas9 off-target sites can be predicted by many bioinformatics tools. Here the authors present low complexity mechanistic model that characterizes SpCas9 kinetics in free-energy terms, allowing quantitative prediction of off-target activity in bulk-biochemistry, single molecule, and whole-genome profiling experiments.

    • Behrouz Eslami-Mossallam
    • , Misha Klein
    •  & Martin Depken

  • Article
    | Open Access

    The rotary ATPases use a rotary catalytic mechanism to drive transmembrane proton movement powered by ATP hydrolysis. Here, the authors report a collection of V/A-ATPase V1 domain structures, providing insights into rotary mechanism of the enzyme and potentially other rotary motor proteins driven by ATP hydrolysis.

    • J. Kishikawa
    • , A. Nakanishi
    •  & K. Yokoyama

  • Article
    | Open Access

    EndoE is a multi-domain glycoside hydrolase of the human pathogen Enterococcus faecalis. Here, the authors present crystal structures of EndoE and provide biochemical insights into the molecular basis of EndoE’s substrate specificity and catalytic mechanism.

    • Mikel García-Alija
    • , Jonathan J. Du
    •  & Marcelo E. Guerin

  • Article
    | Open Access

    Adenylyl cyclases (ACs) generate the second messenger cAMP and play an important role in cellular signaling. Here, the authors use cryo-EM to trace the conformational changes resulting from binding to partial and full activators to one of these enzymes, AC9.

    • Chao Qi
    • , Pia Lavriha
    •  & Volodymyr M. Korkhov

  • Article
    | Open Access

    Human Bloom’s syndrome (BLM) helicase has a role in DNA repair, and BLM deficiency in humans is associated with chromosomal abnormalities. Here the authors employ solution biophysical assays to show BLM maintains a balance for disruption and stabilization of oligonucleotide-based D-loops. Interaction with the Topoisomerase IIIalpha-RMI1-RMI2 complex orients the activity toward D-loop disruption.

    • Gábor M. Harami
    • , János Pálinkás
    •  & Mihály Kovács

  • Article
    | Open Access

    The catalytic domains in nonribosomal peptide synthetases (NRPSs) are responsible for a choreography of events that elongates substrates into natural products. Here, the authors present cryo-EM structures of a siderophore-producing dimeric NRPS elongation module in multiple distinct conformations, which provides insight into the mechanisms of catalytic trajectory.

    • Jialiang Wang
    • , Dandan Li
    •  & Zhijun Wang

  • Article
    | Open Access

    Glycerol-3-phosphate phosphatase is a recently discovered enzyme at the heart of metabolism. Here, the authors used C. elegans and showed that its activation promotes stress resistance, healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility.

    • Elite Possik
    • , Clémence Schmitt
    •  & Marc Prentki

  • Article
    | Open Access

    SxtT and GxtA are Rieske oxygenases that are involved in paralytic shellfish toxin biosynthesis and catalyze monohydroxylation reactions at different positions on the toxin scaffold. Here, the authors present crystal structures of SxtT and GxtA with the native substrates β-saxitoxinol and saxitoxin as well as a Xenon-pressurized structure of GxtA, which reveal a substrate access tunnel to the active site. Through structure-based mutagenesis studies the authors identify six residues in three different protein regions that determine the substrate specificity and site selectivity of SxtT and GxtA. These findings will aid the rational engineering of other Rieske oxygenases.

    • Jianxin Liu
    • , Jiayi Tian
    •  & Jennifer Bridwell-Rabb

  • Article
    | Open Access

    TCPTP is a non-receptor type protein tyrosine phosphatase involved in various signalling pathways. Here, the authors provide structural insights into TCPTP activation, showing that TCPTP is inhibited by its C-terminal tail, which can be displaced by the cytosolic tail of integrin-α1, leading to activation.

    • Jai Prakash Singh
    • , Yang Li
    •  & Tzu-Ching Meng

  • Article
    | Open Access

    Non-heme iron and α-ketoglutarate-dependent (Fe/αKG) oxygenases have attracted attention for their application as biocatalysts due to their flexibility and high efficiency. Here, the authors show the biochemical and structural characterizations of the versatile Fe/αKG oxygenase SptF, involved in the biosynthesis of fungal meroterpenoid emervaridones.

    • Hui Tao
    • , Takahiro Mori
    •  & Ikuro Abe

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