Enzymes articles within Nature Communications

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  • Article
    | Open Access

    Coactivator-associated arginine methyltransferase 1 (CARM1) is an important target in hematologic malignancies. In this work, the authors show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates CARM1 which regulates its methyltransferase activity and alters its target specificity.

    • Hidehiro Itonaga
    • , Adnan K. Mookhtiar
    •  & Stephen D. Nimer

  • Article
    | Open Access

    Reynolds and colleagues examine a biochemically-mediated epistatic interaction between metabolic enzymes involved in folate metabolism and show that biochemical coupling shapes the range of enzyme activities sufficient to rescue cell growth.

    • Thuy N. Nguyen
    • , Christine Ingle
    •  & Kimberly A. Reynolds

  • Article
    | Open Access

    Continuous-flow biocatalysis with immobilized enzymes is a sustainable route for chemical synthesis, but inadequate biocatalytic efficiency caused by non-productive enzyme immobilization or enzyme-carrier mismatches presents a challenge for its application. Here, the authors report an approach for the fabrication of a high-performance enzymatic continuous-flow reactor via integrating scalable isoporous block copolymer membranes as carriers with an oriented one-step enzyme immobilization via a genetically fused material binding peptide.

    • Zhenzhen Zhang
    • , Liang Gao
    •  & Volker Abetz

  • Article
    | Open Access

    Cystathionine beta-synthase is a conserved essential enzyme of one-carbon metabolism. Here, the authors show that the enzyme oligomerises to form filaments that undergo conformational and morphological changes in response to its activator S-adenosyl-L-methionine, the global methyl donor.

    • Thomas J. McCorvie
    • , Douglas Adamoski
    •  & Wyatt W. Yue

  • Article
    | Open Access

    Carbon monoxide dehydrogenases (CODH) employ artificial electron mediators like viologens for biocatalysis, but little is known about the interaction between the mediators and the enzyme. Here, the authors discover the critical site for viologen interactions at the D-cluster of Carboxydothermus hydrogenoformans CODH2 via alanine mutations and crystallography, and report variants with increased ethyl viologen affinity.

    • Suk Min Kim
    • , Sung Heuck Kang
    •  & Yong Hwan Kim

  • Article
    | Open Access

    High-resolution cryo-EM study of human muscle phosphorylase kinase reveals its complex structure and how calcium ions activate it, offering insights into glycogen metabolism and kinase regulation.

    • Xiaoke Yang
    • , Mingqi Zhu
    •  & Junyu Xiao

  • Article
    | Open Access

    Solar-driven artificial food synthesis from CO2 provides an approach to overcome the limitations of natural photosynthesis, but it is very challenging. Here, the authors report a hybrid electrocatalytic-biocatalytic flow system, coupling photovoltaics-powered electrocatalysis (CO2 to formate) with a five enzyme cascade platform (formate to sugar), which achieves conversion of CO2 to C6 sugar (L-sorbose) with a solar-to-food energy conversion efficiency of 3.5%.

    • Guangyu Liu
    • , Yuan Zhong
    •  & Yujie Xiong

  • Article
    | Open Access

    Diels-Alderases (DAs), enzymes catalyzing [4 + 2] cycloaddition reactions, are of high interest, but insights into their evolution are lacking. Here, the authors investigate the evolutionary origins of the intermolecular DAs in the biosynthesis of Moraceae plant-derived Diels-Alder-type secondary metabolites, suggesting they evolved from an ancestor functioning as a flavin adenine dinucleotide-dependent oxidocyclase.

    • Qi Ding
    • , Nianxin Guo
    •  & Xiaoguang Lei

  • Article
    | Open Access

    The pathogen Legionella pneumophila mediates NAD+-dependent ubiquitination pathways upon infection. Here, the authors show the Legionella effector MavL reverses ubiquitin ADP-ribosylation to regulate these pathways. MavL represents a new macrodomain class specific for reversal of arginine ADP-ribosylation with distinct ADP-ribose binding features.

    • Zhengrui Zhang
    • , Jiaqi Fu
    •  & Chittaranjan Das

  • Article
    | Open Access

    Designing complex synthetic materials for enzyme immobilization could unlock the utility of biocatalysis in extreme environments. Here, the authors report on random copolymer brushes as dynamic immobilization supports that enable supra-biological catalytic performance of immobilized enzymes.

    • Héctor Sánchez-Morán
    • , Joel L. Kaar
    •  & Daniel K. Schwartz

  • Article
    | Open Access

    The authors previously showed that a histidine nucleophile and a flexible arginine can work in synergy to accelerate the Morita Baylis-Hillman (MBH) reaction. Here, they report another efficient MBHase that employs a non-canonical Nδ-methylhistidine nucleophile paired with a catalytic glutamate, providing an alternative mechanistic solution for MBH catalysis.

    • Amy E. Hutton
    • , Jake Foster
    •  & Anthony P. Green

  • Article
    | Open Access

    Understanding the complex relationships between enzyme sequence, folding stability and catalytic activity is essential for applications, but current technologies cannot simultaneously resolve both stability and activity phenotypes and couple these to gene sequences at large scale. Here, the authors report Enzyme Proximity Sequencing (EP-Seq), a deep mutational scanning method to assay both expression level and catalytic activity of thousands of oxidoreductase variants from a cellular pool in a single experiment.

    • Rosario Vanella
    • , Christoph Küng
    •  & Michael A. Nash

  • Article
    | Open Access

    Circulating monocytes contribute to the transition to pain chronicity but the molecular events that cause their deployment are still unclear. Using a mouse model of hyperalgesic priming, here the authors show that blood monocytes contribute to the emergence of chronic pain via a mechanism that requires a transient disruption of NAAA-regulated lipid signaling.

    • Yannick Fotio
    • , Alex Mabou Tagne
    •  & Daniele Piomelli

  • Article
    | Open Access

    Poly-γ-glutamate tails are a distinctive feature of folate and F420 cofactors, but it was unclear how these tails elongate while maintaining substrate specificity. Here, the authors discover that folylpolyglutamate synthase and γ-glutamyl ligase enzymes add successive L-glutamates to the termini of the growing γ-glutamyl chain in a processive mechanism.

    • Ghader Bashiri
    • , Esther M. M. Bulloch
    •  & Christopher J. Squire

  • Article
    | Open Access

    Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

    • Elizabeth L. Bell
    • , Gloria Rosetto
    •  & Gregg T. Beckham

  • Article
    | Open Access

    Previous genetically encoded H2O2 probes are based on reversible thiol oxidation. Here, a heme peroxidase is introduced as a thiol-independent H2O2 probe. APEX2 converts H2O2 into fluorescent or luminescent signals, allowing its quantification.

    • Mohammad Eid
    • , Uladzimir Barayeu
    •  & Tobias P. Dick

  • Article
    | Open Access

    Succinate dehydrogenase converts malate to enoloxaloacetate, a metabolically inactive and inhibitory side product of the TCA cycle. Here, Zmuda et al. describe a conserved metabolite damage repair enzyme that can remove enol-oxaloacetate and is critical for efficient aerobic respiration.

    • Anthony J. Zmuda
    • , Xiaojun Kang
    •  & Thomas D. Niehaus

  • Article
    | Open Access

    In vivo detection of cell senescence remains a challenge in aging research. This work introduces a novel fluorogenic probe for β-Gal activity that is excreted in urine, providing a simple diagnosis method to estimate the systemic load of senescent cells during aging and senolytic interventions.

    • Sara Rojas-Vázquez
    • , Beatriz Lozano-Torres
    •  & Ramón Martínez-Máñez

  • Article
    | Open Access

    Much is still unknown of the evolution of animal metabolic enzymes. This study describes a new enzyme family bridging the production of polyketides and membrane lipids. This expands the known biochemical repertoire of animals for making ecologically and biomedically important natural products.

    • Zhenjian Lin
    • , Feng Li
    •  & Eric W. Schmidt

  • Article
    | Open Access

    Here, the authors perform statistical analyses to demonstrate that epistasis is highly pervasive in adaptive evolutionary trajectories of enzymes. Using epistatic data, they expose higher-order rewiring of intramolecular amino acid networks.

    • Karol Buda
    • , Charlotte M. Miton
    •  & Nobuhiko Tokuriki

  • Article
    | Open Access

    Botulinum neurotoxins (BoNTs), the causative agents of the disease botulism, are potent biological toxins. Here the authors use Designed Ankyrin Repeat Proteins (DARPins) to probe BoNT structure and function: DARPin-F5 that completely blocks SNAP25 substrate cleavage by BoNT/A1 in vitro was identified.

    • Oneda Leka
    • , Yufan Wu
    •  & Richard A. Kammerer

  • Article
    | Open Access

    The NLRP3 inflammasome is activated in two steps, priming and assembly, in response to endogenous, microbial, and other environmental danger signals. Here authors show that the assembly step is regulated by acetylation, and inhibition of this post-translational modification prevents full activation of the inflammasome.

    • Yening Zhang
    • , Ling Luo
    •  & Kai Zhao

  • Article
    | Open Access

    Developmental defects in left-right cardiac determination in humans are associated with ciliary dysfunction and low airway epithelial nitric oxide production. Here, the authors show that cytoglobin is essential for nitric oxide signaling, cilia function, and left-right patterning during zebrafish development.

    • Elizabeth R. Rochon
    • , Jianmin Xue
    •  & Paola Corti

  • Article
    | Open Access

    Prediction of enzyme kinetic parameters is essential for designing and optimising enzymes for various biotechnological and industrial applications. Here, authors presented a prediction framework (UniKP), which improves the accuracy of predictions for three enzyme kinetic parameters.

    • Han Yu
    • , Huaxiang Deng
    •  & Xiaozhou Luo

  • Article
    | Open Access

    Type II polyketide synthases (PKSs) normally synthesize polycyclic aromatic compounds, but the potential for the synthesis of further diverse skeletons remains under investigated. Here, the authors report the discovery of the type II PKS machinery for the biosynthesis of a five-membered nonaromatic skeleton contained in the nonproteinogenic amino acid cispentacin and the plant toxin coronatine.

    • Genki Hibi
    • , Taro Shiraishi
    •  & Tomohisa Kuzuyama

  • Article
    | Open Access

    NanoLuc luciferase is a popular bioluminescent enzyme, but the molecular details of its mechanism of action on luciferins such as coelenterazine remained elusive. Here the authors use, protein crystal structures and biochemical analyses to provide an atomistic description of its catalytic mechanism and allosteric behaviour.

    • Michal Nemergut
    • , Daniel Pluskal
    •  & Martin Marek

  • Article
    | Open Access

    Functional annotation of open reading frames in microbial genomes remains substantially incomplete. Here, Kim et al. present a deep learning model that utilizes transformer layers as a neural network architecture to predict specific catalytic functions for enzyme-encoding genes of unknown function.

    • Gi Bae Kim
    • , Ji Yeon Kim
    •  & Sang Yup Lee

  • Article
    | Open Access

    Many AAA+ (ATPases associated with diverse cellular activities) proteins function as a hexamer to remodel protein substrates. Here, the authors report the discovery of a pentameric form of the Lon AAA+ protease and show that it plays a role in the substrate-dependent activation of the AAA+ protein.

    • Shanshan Li
    • , Kan-Yen Hsieh
    •  & Chung-I Chang

  • Article
    | Open Access

    Biological degradation of glycosides involves, alongside hydrolysis, β-elimination for glycosidic bond cleavage. Here, the authors report an O-glycoside β-eliminase from Agrobacterium tumefaciens that converts the C3-oxidized O-β-d-glucoside of phloretin into the aglycone and the 2-hydroxy-3-keto-d-glycal elimination product, and suggest convergent evolution of β-eliminase active sites for the cleavage of natural product 3-keto-O-glycosides.

    • Johannes Bitter
    • , Martin Pfeiffer
    •  & Bernd Nidetzky

  • Article
    | Open Access

    Identification of molecules that induce novel interactions between proteins has been limited by the complexity of rationally designing interactions. The authors report a method to discover molecular glue-like “trimerizers” based on α-helically constrained peptides that can co-opt the surfaces of E3 ubiquitin ligases to bind therapeutically important proteins.

    • Olena S. Tokareva
    • , Kunhua Li
    •  & John H. McGee

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