Enzymes articles within Nature Communications

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  • Article
    | Open Access

    AMP activated protein kinase (AMPK) is a master regulator of cellular metabolism, but how AMPK activity is spatiotemporally regulated remains unclear. Here, Schmitt et al develop a sensitive biosensor for AMPK, which they use to uncover mechanisms for AMPK activity in the lysosome and nucleus.

    • Danielle L. Schmitt
    • , Stephanie D. Curtis
    •  & Jin Zhang

  • Article
    | Open Access

    Haloacid dehalogenase-like phosphatases are widespread across all domains of life and play a crucial role in the regulation of levels of sugar phosphate metabolites in cells. The authors report on the structure-guided engineering of phosphatases for dedicated substrate specificity for the conversion of sucrose and starch into fructose and mannose.

    • Chaoyu Tian
    • , Jiangang Yang
    •  & Yanhe Ma

  • Article
    | Open Access

    The market demand for acarbose, a drug used for treatment of patients affected by type-2 diabetes, has increased. In this article, the authors report the acarbose complete biosynthetic pathway, clarifying previously unknown steps and identifying a pseudoglycosyltransferase enzyme, AcbS, a homologue of AcbI that catalyzes the formation of a non-glycosidic C-N bond.

    • Takeshi Tsunoda
    • , Arash Samadi
    •  & Taifo Mahmud

  • Article
    | Open Access

    Acetohydroxyacid synthase (AHAS) is the target of more than 50 commercial herbicides, with many site-of-action resistance isolates identified in weeds. Here, the authors report the structural and kinetic characterizations to explain the effect AHAS mutations have on herbicide potency.

    • Thierry Lonhienne
    • , Yan Cheng
    •  & Luke W. Guddat

  • 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

    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

    GPI-T catalyzes the committed step in GPI anchor protein biogenesis. Here, Xu et al. report the cryo-EM structure of the human GPI-T, revealing critical elements within an elongated, shared active site which is topologically arranged for substrate specificity.

    • Yidan Xu
    • , Guowen Jia
    •  & Dianfan Li

  • 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

    Darobactin is a ribosomally synthesized and post-translationally modified peptide featuring a unique scaffold and potent activity against Gram-negative bacteria. Here, the authors identify darobactin synthase DarE as responsible for the bicyclic scaffold formation and propose the name daropeptide for this growing class of enzymes.

    • Sijia Guo
    • , Shu Wang
    •  & Qi Zhang

  • Article
    | Open Access

    Cyclic five-membered disulfides (1,2-dithiolanes) have been reported either as nonspecific redox motifs, or as highly specific cellular probes for thioredoxin reductase (TrxR). Here the authors show that 1,2-dithiolane probes are nonspecifically reduced by a range of thiol reductants and are not sensitive to TrxR modulation, thus they are unsuitable as cellular probes for TrxR.

    • Jan G. Felber
    • , Lena Poczka
    •  & Oliver Thorn-Seshold

  • Article
    | Open Access

    Lysine benzoylation (Kbz) is a recently discovered histone modification. Here, the authors characterize writers, erasers and readers of histone Kbz in S. cerevisiae and identify non-histone proteins bearing Kbz, laying foundations to dissect the roles of Kbz in diverse cellular processes.

    • Duo Wang
    • , Fuxiang Yan
    •  & Yong Chen

  • Article
    | Open Access

    Producing plant secondary metabolites by microbes is limited by the known enzymatic reactions. Here, the authors apply machine learning to predict missing link enzymes of benzylisoquinoline alkaloid (BIA) biosynthesis in Papaver somniferum, and validate the specialized activities through heterologous production.

    • Christopher J. Vavricka
    • , Shunsuke Takahashi
    •  & Tomohisa Hasunuma

  • Article
    | Open Access

    Biomolecule-metal-organic-frameworks allow for the creation of hybrid materials with desired biological and chemical function. Here, the authors refine the structure-function relationship by identifying the atomic-layer structure of the hybrids and show differences in structure upon different crystallisation pathways.

    • Linjing Tong
    • , Siming Huang
    •  & Gangfeng Ouyang

  • Article
    | Open Access

    The ergot alkaloids are a class of natural products known for their pharmacologically privileged molecular structure that are used in the treatment of neurological ailments. Here the authors report on the production of the ergot (fungus)-derived therapeutic precursor, D-lysergic acid (DLA), in baker’s yeast.

    • Garrett Wong
    • , Li Rong Lim
    •  & Wen Shan Yew

  • 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 drug AT-527 targets the SARS-CoV-2 replication machinery. Here the authors use Cryo-EM to show how AT-527 inhibits SARS-CoV-2 polymerase by acting as an immediate RNA chain terminator and stably binding in a NiRAN active-site pocket; impeding an essential nucleotide-transfer activity.

    • Ashleigh Shannon
    • , Véronique Fattorini
    •  & Bruno Canard

  • Article
    | Open Access

    Nonribosomal peptide synthetases work with additional enzymes to synthesise secondary metabolites and therapeutics. Here, the authors explore bacillamide D synthesis and show the oxidase action is done while the intermediate is attached to the synthetase and replicate this with an oxidase bound synthetase for bioengineering applications.

    • Camille Marie Fortinez
    • , Kristjan Bloudoff
    •  & T. Martin Schmeing

  • Article
    | Open Access

    The colonic mucus layer is an organized system providing a physical barrier against pathogens and simultaneously harbouring the commensal flora. Here the authors report that transglutaminase 3 activity contributes to homeostasis of the colonic mucus layer and the lack of this enzymatic activity leads to increased susceptibility against DSS-induced colitis in mice.

    • Jack D. A. Sharpen
    • , Brendan Dolan
    •  & Christian V. Recktenwald

  • 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

    Microbial DNA glycosylases associated with the biosynthesis of DNA-damaging antibiotics have evolved self-resistance for their cognate natural products. Here, the authors provide evidence that cellular self-resistance is enabled by reduced affinity of the glycosylases for the excision products of the corresponding DNA lesions.

    • Elwood A. Mullins
    • , Jonathan Dorival
    •  & Brandt F. Eichman

  • Article
    | Open Access

    AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the synthesis of all glycerolipids. Here, the authors show that AGPAT2 and CDP-DAG synthases (CDS1 and CDS2) form functional complexes that promote further conversion of PA along the CDP-DAG pathway of phospholipid synthesis.

    • Hoi Yin Mak
    • , Qian Ouyang
    •  & Hongyuan Yang

  • Article
    | Open Access

    L-asparaginases catalyse the hydrolysis of L-asparagine to L-aspartic acid and ammonia. Here, the authors present high resolution crystal structures of Rhizobium etli L-asparaginase that contains a Zn2+ binding site without a catalytic role and discuss the catalytic mechanism of the enzyme.

    • Joanna I. Loch
    • , Barbara Imiolczyk
    •  & Mariusz Jaskolski

  • Article
    | Open Access

    The nucleotidyl cyclase toxin exoenzyme Y (ExoY), which is secreted by the human pathogens Pseudomonas aeruginosa and Vibrio vulnificus is activated by actin. Here, the authors present the cryo-EM structures of PaExoY bound to F-actin and VvExoY in complex with G-actin-profilin. These structures together with molecular dynamics simulations and enzymatic assays provide insights into the activation mechanism for both bacterial cyclase toxin families that interact with either F- or G-actin.

    • Alexander Belyy
    • , Felipe Merino
    •  & Stefan Raunser

  • Article
    | Open Access

    The modification of proteins with O-linked β-N-acetylglucosamine (OGlcNAc) plays roles in regulation of numerous cellular functions while incorrect O-GlcNAcylation patterns are linked to disease. Here, the authors report a cryo-EM structure of full-length O-GlcNAc transferase (OGT), the only enzyme responsible for O-GlcNAcylation.

    • Richard W. Meek
    • , James N. Blaza
    •  & Gideon J. Davies

  • Article
    | Open Access

    The human 2-oxoglutarate (2OG) oxygenases FIH and AspH are relevant drug targets. Here, the authors show that synthetic and naturally occurring 2OG derivatives can selectively modulate FIH and AspH activities, suggesting that these compounds may serve as a basis to develop 2OG oxygenase-targeting probes and drugs.

    • Yu Nakashima
    • , Lennart Brewitz
    •  & Christopher J. Schofield

  • Article
    | Open Access

    Post-translational modifications are critical for regulating the DNA damage response. Here, the authors identify a methylation-deubiquitination crosstalk between methyltransferase PRMT1 and deubiquitinase USP11, showing that the enzymes regulate each other’s functions in DNA repair.

    • Maria Pilar Sanchez-Bailon
    • , Soo-Youn Choi
    •  & Clare C. Davies

  • Article
    | Open Access

    The Clostridium difficile virulence factors TcdA and TcdB contain a glucosyltransferase domain (GTD), which has both glucohydrolase (GH) and glucosyltransferase (GT) activities. Here, the authors characterize the transition state features of the TcdA and TcdB GH reactions by measuring kinetic isotope effects and they identify two transition state analogues, isofagomine and noeuromycin that inhibit TcdA and TcdB. They also present the crystal structures of TcdB-GTD bound to these inhibitors and the reaction product UDP.

    • Ashleigh S. Paparella
    • , Briana L. Aboulache
    •  & Vern L. Schramm

  • Article
    | Open Access

    Living cells can harvest environmental energy to drive chemical processes. Here the authors design a minimal artificial system that achieves steady states at similar metabolic densities to microorganisms.

    • Andrea Testa
    • , Mirco Dindo
    •  & Paola Laurino

  • Article
    | Open Access

    Legionella pneumophila (LP) employs the metaeffector SidJ to suppress the toxicity of SdeA and other LP SidE effector family members by catalysing the glutamylation of the catalytic Glu residue. Here, the authors present the cryo-EM structures of SidJ in complex with SdeA in two different states, which together with mutagenesis analysis provide insights into the substrate recognition and the mechanism of protein glutamylation by SidJ.

    • Michael Adams
    • , Rahul Sharma
    •  & Sagar Bhogaraju

  • Article
    | Open Access

    Calcineurin — the Ca2+ regulated phosphatase and target of immunosuppressants — regulates GPCR-mediated phospholipid signaling at the plasma membrane. Here the authors show that CNAβ1 (a poorly studied isoform of the calcineurin catalytic subunit) is targeted to the plasma membrane through palmitoylation to dephosphorylate and promote PI4KA complex activity.

    • Idil Ulengin-Talkish
    • , Matthew A. H. Parson
    •  & Martha S. Cyert

  • Article
    | Open Access

    Application of adenine base editors (ABE) has been precluded by low activity. Here the authors show the generation of a human cell based ABE directional screening system and identification of ABE variant (NG-ABEmax-KR) exhibiting a significant increase in activity for human and mouse genome manipulation.

    • Junhao Fu
    • , Qing Li
    •  & Feng Gu

  • Article
    | Open Access

    Enzymes installing an intact hydropersulfide (-SSH) group into natural products have so far not been identified. Here, the authors report the characterization of an S-adenosyl methionine-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin biosynthesis, and identification of three SH domains within several NRPS-PKS assembly lines as thiocysteine lyases.

    • Song Meng
    • , Andrew D. Steele
    •  & Ben Shen

  • Article
    | Open Access

    Soluble guanylate cyclase (sGC) is a validated drug target for cardiovascular diseases. Here, the authors report structures of human sGC in complex with NO and sGC stimulators or activator, providing insight into the mechanism of sGC activation by pharmacological compounds.

    • Rui Liu
    • , Yunlu Kang
    •  & Lei Chen

  • Article
    | Open Access

    Understanding the structure and dynamics of enzymes is important for a number of applications. Here, the authors report on the crystal structure of vanillic acid decarboxylase, and show how the dynamics of the UbiD superfamily enzymes relate to the covalent catalysis of aromatic (de)carboxylation.

    • Stephen A. Marshall
    • , Karl A. P. Payne
    •  & David Leys

  • Article
    | Open Access

    5-Hydroxymethylfurfural (HMF) can be transformed to a range of industrially useful derivatives, such as 2,5-diformylfuran (DFF), but the reactions needed for efficient industrial production are hindered by several issues. Here, the authors perform reaction and enzyme engineering resulting in a galactose oxidase variant with high activity towards HMF, improved oxygen binding and high productivity.

    • William R. Birmingham
    • , Asbjørn Toftgaard Pedersen
    •  & Nicholas J. Turner

  • Article
    | Open Access

    F1Fo ATP synthase works using a rotary catalysis mechanism. Here, the authors report cryo-EM structures of Bacillus PS3 F1-ATPase encompassing the complete set of six states taken up during the catalytic cycle, including the binding- and catalytic-dwell states.

    • Meghna Sobti
    • , Hiroshi Ueno
    •  & Alastair G. Stewart

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