Enzymes articles within Nature Communications

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  • Article
    | Open Access

    Polyketides are typically assembled from a starter unit and malonyl- and/or methylmalonyl-CoA-derived extender units, but the macrolide antibiotics stambomycins incorporate non-standard alkylmalonyl-CoA extender units. Here, the authors describe the biosynthetic pathway responsible for this unusual synthesis.

    • Lauren Ray
    • , Timothy R. Valentic
    •  & Gregory L. Challis

  • Article
    | Open Access

    Antibiotic resistance is common in environmental bacteria, including those living in isolated caves. Here, Pawlowskiet al. study one of these bacterial strains, showing that it is resistant to most clinically used antibiotics through a remarkable variety of mechanisms, some of which are new to science.

    • Andrew C. Pawlowski
    • , Wenliang Wang
    •  & Gerard D. Wright

  • Article
    | Open Access

    Human YME1L is a membrane-anchored AAA+ protease that maintains proteostasis in the mitochondrial inner membrane and intermembrane space. Here the authors probe the substrate-binding and degradation activities of YME1L and suggest the existence of sequence-specific degradation signals in mitochondrial proteostasis.

    • Hui Shi
    • , Anthony J. Rampello
    •  & Steven E. Glynn

  • Article
    | Open Access

    Pyruvate carboxylases are homotetrameric enzymes in eukaryotes and most bacteria. Here, the authors report the structure of an unusual two-subunit form of the enzyme from the Gram-negative bacterium Methylobacillus flagellates, revealing an unexpected α2β4stoichiometry.

    • Philip H. Choi
    • , Jeanyoung Jo
    •  & Liang Tong

  • Article
    | Open Access

    Specialized translation elongation factors (eEFSec and SelB) promote selenocysteine incorporation into proteins. Here, the authors report the structure of human eEFSec, examine its interactions with guanine nucleotides, and propose a non-canonical mechanism for decoding selenocysteine.

    • Malgorzata Dobosz-Bartoszek
    • , Mark H. Pinkerton
    •  & Miljan Simonović

  • Article
    | Open Access

    Homologous recombination requires end resection of the DNA at the site of the break, however the Ku dimer can sequester single-ended double-strand breaks. Here the authors show that ATM-dependent phosphorylation of CtIP, along with the actions of Mre11, impair the stable loading of Ku onto DNA.

    • Pauline Chanut
    • , Sébastien Britton
    •  & Patrick Calsou

  • Article
    | Open Access

    The E3 ligase RNF168 is essential for the signalling of DNA double strand break and its mutations are associated with the RIDDLE syndrome. Here the authors identify TOP2a as substrate for RNF168 and USP10; providing a link between the RNF168/USP10 axis, TOP2a and the response to anti-cancer drugs that target TOP2.

    • Kiran Kumar Naidu Guturi
    • , Miyuki Bohgaki
    •  & Razqallah Hakem

  • Article
    | Open Access

    Chromosomal single-strand DNA breaks occur frequently and require repair to avoid disease outcomes. Here, the authors show that in bird cells, PARP3 accelerates this repair, and use structural biology and cell biology techniques to reveal details of the mechanism of action.

    • Gabrielle J. Grundy
    • , Luis M. Polo
    •  & Keith W. Caldecott

  • Article
    | Open Access

    Bacterial beta-lactamases are responsible for resistance to beta-lactams, the most important family of antibiotics. Here, the authors reveal cyclic boronate inhibitors that are active against both serine- and metallo-beta-lactamases and represent a promising strategy for combined antimicrobial treatments.

    • Jürgen Brem
    • , Ricky Cain
    •  & Christopher J. Schofield

  • Article
    | Open Access

    The stressosome is a multiprotein complex that regulates the expression of stress response genes in Gram-positive bacteria. Here the authors characterize a stressosome from a Gram-negative bacterium, showing that one of the protein components senses oxygen through a bound haem.

    • Xin Jia
    • , Jian-bo Wang
    •  & Emily E. Weinert

  • Article
    | Open Access

    HIV-1 viral gene expression stochastically switches between active and inactive states. Here, using improved single molecule RNA microscopy, the authors show that HIV-1 RNA stochastic transcription is achieved by groups of closely spaced polymerases, and is regulated by Mediator and TBP at different time scales.

    • Katjana Tantale
    • , Florian Mueller
    •  & Edouard Bertrand

  • Article
    | Open Access

    Phosphorylation of L-type calcium CaV channels by protein kinase A is essential for several physiological events. Here, the authors show how this kinase regulates CaV1.4 activity, suggesting a general regulatory mechanism for all L-type calcium channels.

    • Lingjie Sang
    • , Ivy E. Dick
    •  & David T. Yue

  • Article
    | Open Access

    Mutations in the protein LRRK2 have been associated with Parkinson's disease but little is still known about the basic functions of the protein in the brain. Here the authors show that in fruit flies, LRRK2 regulates retrograde homeostatic synaptic compensation at the larval neuromuscular junction.

    • Jay Penney
    • , Kazuya Tsurudome
    •  & A. Pejmun Haghighi

  • Article
    | Open Access

    Claspin mediates the transmission of a replication-stress signal from ATR to Chk1 and is necessary for efficient fork progression. Here the authors demonstrate that the C-terminal acidic patch is important for this role due to its interaction with Cdc7.

    • Chi-Chun Yang
    • , Masahiro Suzuki
    •  & Hisao Masai

  • Article
    | Open Access

    CtBP1-S/BARS is required for fission of endomembrane compartments including the Golgi. Here the authors show that CtBP1-S/BARS activates a trans-Golgi lysophosphatidic acid acyltransferase that catalyses the production of phosphatidic acid and is required for fission of the post-Golgi carrier membrane.

    • Alessandro Pagliuso
    • , Carmen Valente
    •  & Alberto Luini

  • Article
    | Open Access

    The post-transcriptional 5-methylcytosine (m5C) modification occurs in a wide range of nuclear-encoded RNAs. Here the authors identify the mitochondrial tRNA-Met as a target for the m5C methyltransferase NSun3—found mutated in a mitochondrial disease patient—and link mitochondrial tRNA modifications with energy metabolism.

    • Lindsey Van Haute
    • , Sabine Dietmann
    •  & Michal Minczuk

  • Article
    | Open Access

    While reversal of lysine methylation on histone tails is a well-established mechanism to tune gene expression, the existence of a similar arginine demethylation process is controversial. Here, the authors show that some jumonji enzymes possess both lysine and arginine demethylase activity in vitro.

    • Louise J. Walport
    • , Richard J. Hopkinson
    •  & Christopher J. Schofield

  • Article
    | Open Access

    DNA methylation contributes to transcriptional silencing. Here, Groth et al.show that mutant plants defective in MTHFD1, an enzyme involved in folate metabolism, have a DNA hypomethylation phenotype highlighting the link between one-carbon metabolism and DNA methylation, which is mediated by SAM as a common methyl donor.

    • Martin Groth
    • , Guillaume Moissiard
    •  & Steven E. Jacobsen

  • Article
    | Open Access

    Biocatalysis and metal catalysis often provide complimentary reactivities and selectivities. Here, the authors exploit the regioselectivity of an enzymatic C–H activation followed by palladium catalysed carbon-carbon bond formation in one pot, with membrane compartmentalization used to isolate the two chemistries.

    • Jonathan Latham
    • , Jean-Marc Henry
    •  & Jason Micklefield

  • Article
    | Open Access

    Cellulose is produced in plants by cellulose synthase complexes (CSCs) that are assembled in the endomembrane system and then trafficked to the plasma membrane. Here Zhang et al. show that the Golgi-localized STELLO1 and 2 proteins are required for the proper assembly and distribution of CSCs in plant cells.

    • Yi Zhang
    • , Nino Nikolovski
    •  & Paul Dupree

  • Article
    | Open Access

    Squamous epithelia present actin-rich microridges on the apical surface, but the mechanism of their formation is not known. Here the authors show that, in zebrafish epidermis, the exclusion of the basolateral regulator Lgl from the apical domain by atypical protein kinase C prevents precocious elongation and fusion of microridges.

    • Renuka Raman
    • , Indraneel Damle
    •  & Mahendra Sonawane

  • Article
    | Open Access

    The ataxia-telangiectasia mutated (ATM) protein kinase is a key player in the response to DNA damage and is essential for the maintenance of cellular homeostasis. Here the authors describe the cryo-EM structure of ATM/Tel1 from fission yeast that suggests how dimerization regulates its activity.

    • Xuejuan Wang
    • , Huanyu Chu
    •  & Gang Cai

  • Article
    | Open Access

    The cell cycle division protein Cdc45 is required for genome duplication in eukaryotes. Here, the authors determine the crystal structure of human Cdc45 and combine it with functional data to improve our understanding of its role in DNA replication.

    • Aline C. Simon
    • , Vincenzo Sannino
    •  & Luca Pellegrini

  • Article
    | Open Access

    Phytochromes regulate plant responses to environmental light conditions but despite extensive research the initial events in phytochrome signaling remain uncertain. Here, Shin et al. provide evidence that phytochrome phosphorylates target proteins via kinase activity in the N-terminal core domain.

    • Ah-Young Shin
    • , Yun-Jeong Han
    •  & Jeong-Il Kim

  • Article
    | Open Access

    ADAM17 is a member of the ‘Disintegrin and Metalloproteinase’ family of proteases, that cleaves transmembrane substrates from the surfaces of cells. Here the authors show that surface exposure of phosphatidylserine is required for ADAM17 sheddase activity, possibly by directing the protease to its substrates.

    • Anselm Sommer
    • , Felix Kordowski
    •  & Karina Reiss

  • Article
    | Open Access

    Xanthones are pharmacologically and biosynthetically intriguing compounds. Here, the authors identify two cytochrome P450 enzymes, which hydroxylate and cyclize the benzophenone precursor to either 1,3,7- or 1,3,5-trihydroxyxanthones, and pinpoint residues that determine the alternative regioselectivities.

    • Islam El-Awaad
    • , Marco Bocola
    •  & Ludger Beerhues

  • Article
    | Open Access

    The sensitivity of nitrogenase to oxygen is a major barrier to engineer biological nitrogen fixation into cereal crops by direct nif gene transfer. Here the authors use yeast to show that targeting nitrogenase Fe protein to the mitochondrial matrix overcomes the O2sensitivity impediment.

    • Gema López-Torrejón
    • , Emilio Jiménez-Vicente
    •  & Luis M. Rubio

  • Article
    | Open Access

    The membrane-bound kinase CckA controls the activity of the Caulobacter crescentusmaster regulator CtrA, which in turn coordinates asymmetric cell division. Here, the authors show that CckA contains two sensory domains that have distinct sensitivities to fluctuations in cyclic-di-GMP concentration and subcellular niche.

    • Thomas H. Mann
    • , W. Seth Childers
    •  & Lucy Shapiro

  • Article
    | Open Access

    Class I histone deacetylase complexes can be activated by inositol phosphates. Here, the authors investigate the stereochemical requirements for activation; use the crystal structure to understand substrate recognition, and suggest an entropically driven mechanism of allostery.

    • Peter J. Watson
    • , Christopher J. Millard
    •  & John W. R. Schwabe

  • Article
    | Open Access

    Antibiotic resistance is a major clinical problem that threatens to undermine our ability to control infectious diseases. Here the authors present detailed structural analysis of Rifampin phosphotransferase from Listeria monocytogenes, yielding insight on how this class of enzyme inactivates its target antibiotics.

    • Peter J. Stogios
    • , Georgina Cox
    •  & Gerard D. Wright

  • Article
    | Open Access

    Acetyl-CoA carboxylases are central regulatory hubs of fatty acid metabolism and are important targets for drug development in obesity and cancer. Here, the authors demonstrate that the regulation of these highly dynamic enzymes in fungi is governed by a mechanism based on phosphorylation-dependent conformational variability.

    • Moritz Hunkeler
    • , Edward Stuttfeld
    •  & Timm Maier

  • Article
    | Open Access

    The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a wide range of anabolic and catabolic processes. Here the authors describe a sub-nanometer cryo-EM structure of a yeast Tor–Lst8 complex and propose an overall topology that differs from that previously suggested for mTORC1.

    • Domagoj Baretić
    • , Alex Berndt
    •  & Roger L. Williams

  • Article
    | Open Access

    Ras signalling through PI3K kinase has an important role in tumour initiation and progression. Here, the authors show that the interaction of Ras with PI3-Kinase p110α and the subsequent activation of Rac-GTPase impairs cell -cell interaction by blocking the downstream Reelin/E-cadherin, thus resulting in cell migration.

    • Esther Castellano
    • , Miriam Molina-Arcas
    •  & Julian Downward

  • Article
    | Open Access

    PDE6δ regulates the sorting of prenylated cargo proteins. Here Fansa et al. propose that the affinity of the interaction between PDE6δ and its cargo protein determines whether they are released by cytoplasmic or cilia-specific release factors ultimately determining their subcellular localization.

    • Eyad Kalawy Fansa
    • , Stefanie Kristine Kösling
    •  & Shehab Ismail

  • Article
    | Open Access

    The green microalga Botryococcus braunii is a promising biofuel producer due to its ability to produce large amounts of hydrocarbon oils that can be converted into fuels. Here the authors implicate lycopaoctaene synthase, a squalene synthases-like enzyme, in the first step towards the biosynthesis of the C40 tetraterpenoid hydrocarbon lycopadiene.

    • Hem R. Thapa
    • , Mandar T. Naik
    •  & Timothy P. Devarenne

  • Article
    | Open Access

    The protein kinase ASK1 has been linked to cellular stress responses. Here the authors show that ASK1 also regulates gene expression and activity of beige and brown adipocytes, and demonstrate adipocyte ASK1 has a physiological role in regulating thermogenesis in mice.

    • Kazuki Hattori
    • , Isao Naguro
    •  & Hidenori Ichijo

  • Article
    | Open Access

    Deregulation of lipid metabolism in cancer cells is critical to the maintenance of certain malignant features. Here, the authors show that the proliferation of breast cancer cells depends upon the extracellular activity of the endothelial lipase enzyme LIPG whose expression is regulated by the FoxA family of transcription factors.

    • Felipe Slebe
    • , Federico Rojo
    •  & Roger R. Gomis

  • Article
    | Open Access

    Ternary complex (TC) and eIF4F complex assembly are rate-limiting steps in translation initiation that are regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway. Here the authors show that the protein kinases mTORC1 and CK2 coordinate TC and eIF4F complex assembly through eIF2β to stimulate cell proliferation.

    • Valentina Gandin
    • , Laia Masvidal
    •  & Ivan Topisirovic

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