Enzyme mechanisms articles within Nature Communications

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  • Article
    | Open Access

    Auxilliary Activity Family 5 (AA5) comprises mononuclear copper radical oxidases with catalytic diversity that is not well characterised. Here, structural, phylogenetic and biochemical analyses advance our understanding of the potential biological and biotechnology functions of these proteins.

    • DeLu (Tyler) Yin
    • , Saioa Urresti
    •  & Harry Brumer

  • Article
    | Open Access

    Diacylglycerol kinase is a small bacterial membrane-bound trimer that catalyses diacylglycerol conversion to phosphatidic acid. Here, the authors solve the crystal structure of the kinase bound to a lipid substrate and an ATP analogue, and show that the active site arose through convergent evolution.

    • Dianfan Li
    • , Phillip J. Stansfeld
    •  & Martin Caffrey

  • Article |

    Slow-dividing ‘loser’ cells are outcompeted by more robust ‘winner’ cells and eliminated by macrophage-like haemocytes in the fruit fly larva. Here the authors show that the dying loser cells secrete the enzyme Tyrosyl-tRNA synthetase that upon Mmp2-mediated cleavage acts as a haemocyte chemoattractant.

    • Sergio Casas-Tintó
    • , Fidel-Nicolás Lolo
    •  & Eduardo Moreno

  • Article
    | Open Access

    RNA-binding proteins (RBPs) are implicated in many biological functions. Here the authors expand the human and yeast RNA interactome identifying new and conserved RBPs, several of which with no prior function assigned to RNA biology or structural motifs known to mediate RNA-binding, and suggesting new roles of RNA as modulators of protein function.

    • Benedikt M. Beckmann
    • , Rastislav Horos
    •  & Matthias W. Hentze

  • Article
    | Open Access

    The SAD kinases contain a UBA domain that binds to the kinase domain and has a role in autoinhibition and allosteric activation of the AMPK homoenzyme. Here, the authors identify an autoinhibitory sequence in SAD and show that the UBA domain synergistically functions as an autoinhibitory domain.

    • Jing-Xiang Wu
    • , Yun-Sheng Cheng
    •  & Jia-Wei Wu

  • Article
    | Open Access

    Rho kinases regulate the actin cytoskeleton by controlling stress fibre formation. Truebestein et al.show that the length of its coiled-coil determines ROCK2 function, and propose that the coiled coil acts as a spacer, targeting kinase activity to a discrete distance from the membrane.

    • Linda Truebestein
    • , Daniel J. Elsner
    •  & Thomas A. Leonard

  • Article
    | Open Access

    The CO2-fixing enzyme rubisco requires motor proteins known as rubisco activases to remove inhibitors bound to its active site. Here the authors describe a new class of rubisco activase present in chemoautotrophic bacteria that belongs to the MoxR family of AAA+ ATPases.

    • Yi-Chin Candace Tsai
    • , Maria Claribel Lapina
    •  & Oliver Mueller-Cajar

  • Article
    | Open Access

    Jmjd6 is a dioxygenase that catalyses lysyl hydroxylation of splicing regulatory proteins. Here the authors show that Jmjd6 directs splicing of a central tolerance regulator Aire in medullary thymic epithelial cells, and that Jmjd6 deficiency leads to loss of Aire and multi-organ autoimmunity in mice.

    • Toyoshi Yanagihara
    • , Fumiyuki Sanematsu
    •  & Fukui Yoshinori

  • Article
    | Open Access

    Evidence suggests that the TCA cycle enzyme complex succinate dehydrogenase (SDH) may be dispensable for cell proliferation in some cancer cells. Here the authors show that SDH deficient cells become dependent on the mitochondrial enzyme pyruvate carboxylase for aspartate production and proliferation.

    • Charlotte Lussey-Lepoutre
    • , Kate E. R. Hollinshead
    •  & Daniel A. Tennant

  • Article
    | Open Access

    Tenuazonic acid is a mycotoxin produced by various plant pathogenic fungi but its biosynthetic gene is unknown to date. Here, the authors identify the tenuazonic acid biosynthetic gene encoding a protein with a unique KS domain that conducts cyclization step for tenuazonic acid release in Magnaporthe oryzae.

    • Choong-Soo Yun
    • , Takayuki Motoyama
    •  & Hiroyuki Osada

  • Article
    | Open Access

    The MARTX toxin of V. choleraeprocesses itself to deliver three distinct effector domains to the cytosol. Here the authors show that the third effector domain is a phosphatidylinositol-3-phosphate (PtdIns3P)-specific phospholipase that inhibits autophagy in target cells.

    • Shivani Agarwal
    • , Hyunjin Kim
    •  & Karla J. F. Satchell

  • Article
    | Open Access

    CDP-alcohol phosphotransferases (CDP-APs) are critical for the biosynthesis of glycerophospholipids. Here, Clarke et al.present the first structure of an enzymatically active CDP-AP in the presence of a bound lipid substrate and propose a mechanism for substrate binding and catalysis.

    • Oliver B. Clarke
    • , David Tomasek
    •  & Filippo Mancia

  • Article
    | Open Access

    The 26S proteasome contains a hexamer of ATPase subunits, which binds, unfolds and translocates substrates in an ATP-dependent manner. Kim et al. use FRET to show that ATP binding preferentially occurs at neighbouring subunits of the hexamer, and identify two allosteric systems that coordinate translocation.

    • Young-Chan Kim
    • , Aaron Snoberger
    •  & David M. Smith

  • Article
    | Open Access

    Cobalamin-dependent radical SAM enzymes are proposed as methyltransferases in many biosynthetic pathways. Here, the authors study a pathway involving the methylation of tryptophan, showing that methylcob(III)alamin is the most likely cofactor and propose a radical-based C-methylation mechanism.

    • Alhosna Benjdia
    • , Stéphane Pierre
    •  & Olivier Berteau

  • Article
    | Open Access

    The availability of crystal structures of photosystem II opens up the possibility of gaining insights into its mechanism. Here, the authors use a computational approach and propose a deprotonation event at O4 followed by long-range proton-transfer along a chain of strongly bonded water molecules.

    • Keisuke Saito
    • , A. William Rutherford
    •  & Hiroshi Ishikita

  • Article
    | Open Access

    During herbivory, deglycosylation of glycosylated phytochemicals may release aglycones which can be toxic when ingested. Here, Poreddy et al. show that ß-glucosidase in the tobacco hornworm midgut converts a toxic glycoside to a non-toxic form, a process which is crucial for larval development.

    • Spoorthi Poreddy
    • , Sirsha Mitra
    •  & Sagar S. Pandit

  • Article
    | Open Access

    n-Butanol is a valuable biofuel that can be produced industrially by bacterial fermentation. Here the authors uncover a redox-switch within Clostridium acetobutylicum’s thiolase—a key enzyme involved in n-butanol biosynthesis—that controls the rate of fermentative butanol production.

    • Sangwoo Kim
    • , Yu-Sin Jang
    •  & Kyung-Jin Kim

  • Article
    | Open Access

    Inhibiting the formation of S-adenosyl-methionine (SAM) increases worm but not fly lifespan. Here the authors show that humans and flies possess the SAM-consuming enzyme Gnmt, the activity of which is regulated by lifespan-extending interventions, and that knockdown of Gnmt extends fly lifespan.

    • Fumiaki Obata
    •  & Masayuki Miura

  • Article
    | Open Access

    Coenzyme B12 traditionally acts as cofactor to light-independent metabolic enzymes in bacteria and humans. Here, Kutta et al.present a time-resolved photochemical description of a B12-dependent photoreceptor protein, which represents a mechanistic foundation for B12 photobiology.

    • Roger J. Kutta
    • , Samantha J. O. Hardman
    •  & Alex R. Jones

  • Article
    | Open Access

    Mycobacterium tuberculosis feeds on host fatty acids during infection, a process that requires a fructose bisphosphatase (FBPase) enzyme for gluconeogenesis. Here, Ganapathy et al.show that the bacterium has two different FBPases and that this enzymatic activity is required for full virulence.

    • Uday Ganapathy
    • , Joeli Marrero
    •  & Sabine Ehrt

  • Article
    | Open Access

    The protein kinase MEKK3 interacts with CCM2, which is associated with the predominantly cerebrovascular CCM disease. Here the authors use structural, biochemical, cell biology and in vivotechniques to show that regulation of Rho signalling by the CCM2:MEKK3 complex is needed to maintain neurovascular integrity.

    • Oriana S. Fisher
    • , Hanqiang Deng
    •  & Bing Su

  • Article
    | Open Access

    9-O-Acetylation is one of the most common modifications of sialic acids, implicated in sialoglycan recognition and ganglioside biology. Here, the authors show that the key enzyme for the biosynthesis of 9-O-acetylated sialoglycans is CASD1, which uses CMP-activated sialic acid as acceptor substrate.

    • Anna-Maria T. Baumann
    • , Mark J. G. Bakkers
    •  & Martina Mühlenhoff

  • Article
    | Open Access

    Synthetic engineering of complex pathways is often hindered by pathway branching and generation of non-target compounds. Here, the authors show that by judicious combination of moderately selective enzyme variants, a non-natural C50 carotenoid can be generated in bacteria with minimal production of unwanted compounds.

    • Maiko Furubayashi
    • , Mayu Ikezumi
    •  & Daisuke Umeno

  • Article
    | Open Access

    Mucosal sialoglycans contribute to host–microbe interactions at mucosal surfaces and impact bacterial colonization of the digestive system. Here the authors identify and characterize an intramolecular trans-sialidase produced by the gut bacterium R. gnavusATCC 29149 that may contribute to adaptation to the mucosal environment.

    • Louise E. Tailford
    • , C. David Owen
    •  & Nathalie Juge

  • Article
    | Open Access

    Upf1 is a multifunctional helicase involved in various DNA- and RNA-related processes, including nonsense-mediated mRNA decay (NMD). Here the authors demonstrate that Upf1 is a highly processive ribonucleoprotein complex remodeler—a capability likely important for Upf1’s NMD function.

    • Francesca Fiorini
    • , Debjani Bagchi
    •  & Vincent Croquette

  • Article
    | Open Access

    Adenylate kinase (AdK) plays a key role in cellular energy homeostasis by catalysing the reversible magnesium-dependent formation of ADP from AMP and ATP. Here the authors present a detailed analysis of adenylate kinase’s conformational dynamics and characterize a high-energy state of AdK indispensable for catalysis.

    • Michael Kovermann
    • , Jörgen Ådén
    •  & Magnus Wolf-Watz

  • Article
    | Open Access

    Kinamycins, fluostatins and lomaiviticins are naturally occurring antibiotics that possess unique diazofluorene structures and exhibit potent anti-tumour activity. Here the authors identify the epoxy hydrolases in the biosynthetic pathways of kinamycins and lomaiviticins, suggesting the existence of epoxy-intermediates in their biosynthesis.

    • Bin Wang
    • , Fang Guo
    •  & Keqian Yang

  • Article
    | Open Access

    Sirtuins are NAD+-dependent deacylases implicated in the regulation of stress responses, bioenergetics and epigenetic control. Here the authors describe the crystal structure of a sirtuin-activating compounds (STAC)-sirtuin complex and begin to elucidate the mechanism of sirtuins activation by STACs.

    • Han Dai
    • , April W. Case
    •  & James L. Ellis

  • Article
    | Open Access

    DNA intercalators, a type of fluorescent probes widely used to visualize DNA, can perturb DNA structure and stability. Here, the authors show how DNA-binding affinity can be tuned using DNA tension, ionic strength and dye species, and how this can be used to minimize DNA structural perturbations.

    • Andreas S. Biebricher
    • , Iddo Heller
    •  & Gijs J. L. Wuite

  • Article |

    Photolyase is an enzyme responsible for repairing DNA which is damaged after exposure to UV light. Here, the authors use site directed mutagenesis and femtosecond spectroscopy to study how photolyase achieves its maximal repair efficiency.

    • Chuang Tan
    • , Zheyun Liu
    •  & Dongping Zhong

  • Article
    | Open Access

    The twin-arginine translocation complex consists of TatA, TatB and TatC subunits and transports folded proteins across cellular membranes. Here, using photocrosslinking, the authors show that TatB monomers form dome-like structures that are surrounded by TatC monomers enabling lateral access of TatA.

    • Anne-Sophie Blümmel
    • , Laura A. Haag
    •  & Julia Fröbel

  • Article
    | Open Access

    V. vulnificus, a bacteria that cause life-threatening septicaemia following wound infections or tainted food consumption, utilizes MARTX toxins for toxic effector delivery. Here the authors show that the MARTX virulence factor DUF5 targets the cellular MAP kinase pathway as a Ras and Rap1 site-specific protease.

    • Irena Antic
    • , Marco Biancucci
    •  & Karla J. F. Satchell

  • Article |

    INO80-C and SWR-C are chromatin remodelling enzymes with roles in transcription pathways. Here, the authors show that they both have similar architectures displaying a ‘tail’ domain and a heterohexameric ‘head’ domain, with conformational changes influencing nucleosomal binding and enzyme activity.

    • Shinya Watanabe
    • , Dongyan Tan
    •  & Craig L. Peterson

  • Article
    | Open Access

    The redox activity of cytochrome cin complex with its peroxidase has been rationalized by two possible models; a readily observable high-affinity complex and a more elusive but potentially more active low-affinity complex. Here, the authors provide an NMR-based structural mapping of this low-affinity complex.

    • Karen Van de Water
    • , Yann G. J. Sterckx
    •  & Alexander N. Volkov

  • Article
    | Open Access

    Most radical SAM enzymes use a [4Fe-4S] cluster to generate a 5′-deoxyadenosyl radical. Here the authors show the radical SAM thiamin pyrimidine synthase ThiC comprises an additional active site metal, probably representing an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.

    • Michael K. Fenwick
    • , Angad P. Mehta
    •  & Steven E. Ealick

  • Article
    | Open Access

    Aldehydes are common intermediates in enzymatic pathways, but their high reactivity can make them difficult to observe. Here, the authors study the mechanism of aldehyde deactivation in a dehydrogenase, showing a key E/Zisomerization and observing a thiohemiacetal intermediate by crystal structure analysis.

    • Lu Huo
    • , Ian Davis
    •  & Aimin Liu

  • Article
    | Open Access

    Many cellular processes, including the cell division cycle, require concerted action of protein kinases and phosphatases. Here Lipinszki et al. present a crystal structure of the Drosophilaphosphoprotein phosphatase 4 subunit, Falafel, in complex with the centromeric protein CENP-C, and reveal a new recognition mode for this phosphatase.

    • Zoltan Lipinszki
    • , Stephane Lefevre
    •  & Marcin R. Przewloka

  • Article |

    The poly(ADP-ribose) polymerase family of enzymes control many aspects of cellular signalling by covalently modifying proteins with either poly- or mono-(ADP-ribose). Vyas et al.catalogue the catalytic specificity of this family, and reveal that the majority of these enzymes generate only mono(ADP-ribose).

    • Sejal Vyas
    • , Ivan Matic
    •  & Paul Chang

  • Article |

    DNA polymerase θ (Pol θ) exhibits properties typical of translesion and repair synthesis; however, its physiological function remains elusive. Here, the authors show that Pol θ plays a role in the initiation and timing of DNA replication during human cell division.

    • Anne Fernandez-Vidal
    • , Laure Guitton-Sert
    •  & Jean-Sébastien Hoffmann

  • Article
    | Open Access

    Cytidine-diphosphate diacylglycerol (CDP-DAG) is a central liponucleotide intermediate required for the biosynthesis of some phospholipids and is synthesized by CDP-DAG synthetase (Cds). Here, Liu et al. report the structure of a Cds that shows how it can accept hydrophilic and hydrophobic substrates, and suggest a mechanism that requires two metal ions.

    • Xiuying Liu
    • , Yan Yin
    •  & Zhenfeng Liu

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