Enzyme mechanisms articles within Nature Communications

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  • Article
    | Open Access

    Carbapenem-resistant bacteria pose a major health threat by expressing metallo-β-lactamases (MβLs), enzymes able to hydrolyse these life-saving drugs. Here the authors use biophysical and computational methods and show that different MβLs share the same reaction mechanism, suggesting new strategies for drug design.

    • María-Natalia Lisa
    • , Antonela R. Palacios
    •  & Alejandro J. Vila

  • Article
    | Open Access

    DNA polymerase (pol) μ functions in DNA double-strand break repair. Here the authors use time-lapse X-ray crystallography to capture the states of pol µ during the conversion from pre-catalytic to product complex and observe a third transiently bound metal ion in the product state.

    • Joonas A. Jamsen
    • , William A. Beard
    •  & Samuel H. Wilson

  • Article
    | Open Access

    HHARI is a RING-in-between-RING (RBR) ubiquitin (Ub) E3 ligase. Here the authors present the crystal structure of HHARI with the UbcH7 ~ Ub thioester intermediate mimetic, which reveals that HHARI binds this E2 ~ Ub in an open conformation and explains the specificity of this cognate RBR E3/E2 pair.

    • Lingmin Yuan
    • , Zongyang Lv
    •  & Shaun K. Olsen

  • Article
    | Open Access

    POGLUT1 is a protein-O-glucosyltransferase that transfers glucose and xylose to the EGF-like domains of Notch and other signaling receptors. Here the authors report the structure of human POGLUT1 in complexes with 3 different EGF-like domains and donor substrates and shed light on the enzyme’s substrate specificity and catalytic mechanism

    • Zhijie Li
    • , Michael Fischer
    •  & James M. Rini

  • Article
    | Open Access

    The generation of glycolipid dolichylphosphate mannose (Dol-P-Man) is a critical step for protein glycosylation and GPI anchor synthesis. Here the authors report the structure of dolichylphosphate mannose synthase in complex with bound nucleotide and donor to provide insight into the mechanism of Dol-P-Man synthesis.

    • Rosaria Gandini
    • , Tom Reichenbach
    •  & Christina Divne

  • Article
    | Open Access

    Of the four intermediates in the catalytic cycle of [FeFe]-hydrogenases, the hydride state still has eluded characterization. Here, the authors shift the reaction equilibrium for three hydrogenases and enrich the hydride-bound species, characterizing them using a real-time IR spectroscopic technique.

    • Martin Winkler
    • , Moritz Senger
    •  & Thomas Happe

  • Article
    | Open Access

    Due to their transient nature, enzyme-substrate complexes are difficult to characterize structurally. Here, the authors capture the reactive reduced form of xenobiotic reductase A bound to its substrate and show that the oxidation state of the flavin cofactor affects the interaction of the substrate with the enzyme.

    • Tobias Werther
    • , Stefan Wahlefeld
    •  & Holger Dobbek

  • Article
    | Open Access

    Lipoproteins are essential components of bacterial membranes. Here the authors present the crystal structures ofPseudomonas aeruginosa and Escherichia coliapolipoprotein N-acyltransferase, which catalyses the final step in the lipoprotein synthesis pathway, and give insights into its mechanism.

    • Maciej Wiktor
    • , Dietmar Weichert
    •  & Martin Caffrey

  • Article
    | Open Access

    Cobalamin-containing reductive dehalogenases from organohalide-respiring bacteria play a key role in the degradation of halogenated organic compounds. Here the authors proposed a catalytic mechanism for dehalogenation that relies on a long-range electron transfer from the cobalt in the centre of the enzyme’s cofactor to the substrate.

    • Cindy Kunze
    • , Martin Bommer
    •  & Gabriele Diekert

  • Article
    | Open Access

    Flap Endonuclease 1 is a DNA replication and repair enzyme indispensable for maintaining genomic stability. Here the authors provide mechanistic details on how FEN1 selects for 5′-flaps and promotes catalysis to avoid large-scale repeat expansion by a process termed ‘phosphate steering’.

    • Susan E. Tsutakawa
    • , Mark J. Thompson
    •  & John A. Tainer

  • Article
    | Open Access

    Chromatin remodellers usually mobilize or disassemble nucleosomes by translocating along the nucleosomal DNA at the H3-H4 interface. Here, the authors provide evidence chromatin remodeller INO80 translocates along DNA at the H2A-H2B interface and displaces DNA from the surface of H2A-H2B.

    • Sandipan Brahma
    • , Maheshi I. Udugama
    •  & Blaine Bartholomew

  • Article
    | Open Access

    Ca2+/calmodulin-dependent protein kinase II (CaMKII) forms a 12 subunit holoenzyme central to synaptic plasticity. Here the authors report a 3D structure of the CaMKII holoenzyme in an activation-competent state obtained by single particle EM, and suggest a role for the intrinsically disordered linker domain in facilitating cooperative activation.

    • Janette B. Myers
    • , Vincent Zaegel
    •  & Steve L. Reichow

  • Article
    | Open Access

    Although all known RNA polymerases have multiple subunits, unrelated single-subunit polymerases have also been described. Here, the authors describe a single-subunit RNA polymerase from the SPβ prophage ofBacillus subtilis, which shares homology to multi-subunit enzymes.

    • David Forrest
    • , Katherine James
    •  & Nikolay Zenkin

  • Article
    | Open Access

    MxA (myxovirus resistance protein A) is a viral restriction factor whose activity depends on self-assembly into polymeric rings and helical filaments. Here the authors reveal the conformational movements involved in generating torque within polymeric MxA molecules and the dynamic conformational changes that occur upon GTP loading and hydrolysis.

    • Yang Chen
    • , Lei Zhang
    •  & Song Gao

  • Article
    | Open Access

    Nonribosomal peptides are important bioactive molecules that are synthetized by enzymes containing several catalytic domains. Here the authors describe the catalytic mechanism of fungal nonribosomal peptide synthetases and present an approach to modify these enzymes to produce specific nonribosomal peptides.

    • Dayu Yu
    • , Fuchao Xu
    •  & Jixun Zhan

  • Article
    | Open Access

    Polyamines bind to nucleic acids and their function is regulated by reversible acetylation. Here, the authors show that histone deacetylase 10 is a polyamine deacetylase and present its crystal structure with a bound polyamine transition state analogue inhibitor.

    • Yang Hai
    • , Stephen A. Shinsky
    •  & David W. Christianson

  • Article
    | Open Access

    The deacetylase Sirt1, known to regulate many cellular functions, can be activated by energy deprivation, however the mechanism is unclear. Here, the authors show that ATP inhibits Sirt1 by binding to the C-terminal domain, and energy deprivation derepresses Sirt1 activity by lowering the ATP level.

    • Hyeog Kang
    • , Shinichi Oka
    •  & Jay H. Chung

  • Article
    | Open Access

    Bacterial type IVa pili are protein filaments used for motility and protein secretion. Here the authors present crystal structures of theGeobacter metallireducensPilB ATPase in two nucleotide states, and suggest a clockwise rotation of the central sub-pores of PilB that would support the assembly of a right-handed helical pilus.

    • Matthew McCallum
    • , Stephanie Tammam
    •  & P. Lynne Howell

  • Article
    | Open Access

    Cytidine deaminases are evolutionarily conserved enzymes that edit genomes by deaminating cytidine to uridine. Here the authors present the crystal structure of APOBEC3A with a single-stranded DNA substrate bound in the active site to shed light on the mechanism and specificity of substrate recognition.

    • Takahide Kouno
    • , Tania V. Silvas
    •  & Celia A. Schiffer

  • Article
    | Open Access

    Glutaredoxins have important roles in redox processes. Here the authors show that the enzymatic activity of glutaredoxins requires two distinct glutathione interactions sites, one recognizing the glutathione disulfide substrate and one activating glutathione as a reducing agent.

    • Patricia Begas
    • , Linda Liedgens
    •  & Marcel Deponte

  • Article
    | Open Access

    River blindness, a disease affecting millions throughout the tropics, is caused by parasitic worms. Here, Yuet al. report the discovery and structural characterization of potent macrocyclic peptide inhibitors of iPGM, a nematode-specific phosphoglycerate mutase, as potential leads for novel antimicrobial agents.

    • Hao Yu
    • , Patricia Dranchak
    •  & James Inglese

  • Article
    | Open Access

    The majority of enzymatic Kemp elimination reactions proceed via a well-established acid-base mechanism. Here, the authors show that cytochrome P450 is able to metabolize the leflunomide drug via a redox Kemp elimination, offering new insights into enzyme catalysis.

    • Aitao Li
    • , Binju Wang
    •  & Manfred T. Reetz

  • Article
    | Open Access

    The N-end rule pathway targets substrate proteins for proteasomal degradation. Here, Whiteet al. show that ArabidopsisPLANT CYSTEINE OXIDASEs show dioxygenase activity producing Cys-sulfinic acid at the N-terminus of target proteins, which then act as direct substrates for arginyl transferase.

    • Mark D. White
    • , Maria Klecker
    •  & Emily Flashman

  • Article
    | Open Access

    Parkin and PINK1 are involved in damaged mitochondria clearance; however the sequence of events of Parkin activation is not clear. Here, the authors show that binding to phospho-ubiquitin on mitochondria enables Parkin phosphorylation, which allows Repressor Element of Parkin removal, E3 ligase activation and mitophagy.

    • Matthew Y. Tang
    • , Marta Vranas
    •  & Edward A. Fon

  • Article
    | Open Access

    Farnesyl pyrophosphate (FPP) is a key building block for the synthesis of many lipids. Here the authors determine the crystal structure of farnesyl pyrophosphate synthase (FPPS) with its bound product and use kinetic measurements to show that FPP is an allosteric effector of the enzyme.

    • Jaeok Park
    • , Michal Zielinski
    •  & Albert M. Berghuis

  • Article
    | Open Access

    The functions of the highly reduced mitochondria (mitosomes) of microsporidians are not well-characterized. Here, the authors show that theTrachipleistophora hominismitosome is the site of iron–sulfur cluster assembly and that its retention is likely linked to its role in cytosolic and nuclear iron–sulfur protein maturation.

    • Sven-A. Freibert
    • , Alina V. Goldberg
    •  & Roland Lill

  • Article
    | Open Access

    Mechanosensation by biological membranes can be relayed by mechanical tension to ion channels. Here the authors show that phospholipase D (PLD) is activated by mechanical disruption of lipid rafts which allows PLD to mix with its substrate in the lipid membrane, and propose a kinetic model of force transduction.

    • E. Nicholas Petersen
    • , Hae-Won Chung
    •  & Scott B. Hansen

  • Article
    | Open Access

    In some parasites, membrane-bound pyrophosphatases, which couple proton and sodium ion transport across the membrane, are important for infectivity. Here, the authors report crystal structures of these proteins alongside biophysical analyses that allow them to propose a model for how the coupling is achieved.

    • Kun-Mou Li
    • , Craig Wilkinson
    •  & Adrian Goldman

  • Article
    | Open Access

    The nature of the ferryl intermediate generated in reactions catalysed by heme-containing enzymes is uncertain, due to the ambiguity of X-ray crystallography data. Here, the authors apply neutron diffraction, kinetics and other spectroscopy to directly observe a protonated ferryl intermediate in a heme peroxidase.

    • Hanna Kwon
    • , Jaswir Basran
    •  & Emma L. Raven

  • Article
    | Open Access

    How archaeal viruses perturb host transcription machinery is poorly understood. Here, the authors provide evidence that the archaeo-viral transcription factor ORF145/RIP targets host RNA polymerase, repressing its activity.

    • Carol Sheppard
    • , Fabian Blombach
    •  & Finn Werner

  • Article
    | Open Access

    KDM4 histone demethylases target specific chromatin regions by a mechanism that is not fully characterised. Here, the authors identify trimethyl-lysine histone-binding preferences for closely related KDM4 double tudor domains and use structural and biochemical information to examine the molecular details of this interaction.

    • Zhangli Su
    • , Fengbin Wang
    •  & John M. Denu

  • Article
    | Open Access

    In bacteria, CRISPR-Cas9 identifies and cleaves the target DNA with the assistance of a tracrRNA and a crRNA. Here the authors use single-molecule spectroscopy to investigate conformational changes and show that the tracrRNA keeps Cas9 in a functionally active form.

    • Youngbin Lim
    • , So Young Bak
    •  & Seong Keun Kim

  • Article
    | Open Access

    Protein Disulfide Isomerase (PDI) is a prothrombotic, multidomain enzyme with separate substrate binding and catalytic domains. Here, the authors identify a new class of compounds that target the PDI substrate binding site, inducing a conformational change in the catalytic domains and inhibiting thrombosis.

    • Roelof H. Bekendam
    • , Pavan K. Bendapudi
    •  & Robert Flaumenhaft

  • Article
    | Open Access

    The response to hypoxia involves multiple genes regulated by the hypoxia inducible transcription factors (HIFs), whose stability is regulated by prolyl hydroxylation. Here the authors provide a molecular basis for the substrate selectivity of the HIF prolyl hydroxylases that can be altered in erythrocytosis and cancer.

    • Rasheduzzaman Chowdhury
    • , Ivanhoe K. H. Leung
    •  & Christopher J. Schofield

  • Article
    | Open Access

    The saw-scaled viper venom causes continued tissue damage that may cause death. Here the authors show that the venom attracts neutrophils to the bite site and induces neutrophil extracellular traps that capture venom components causing tissue damage, which can be prevented by enzymatic DNA degradation.

    • Gajanan D. Katkar
    • , Mahalingam S. Sundaram
    •  & Kempaiah Kemparaju

  • Article
    | Open Access

    Adenylate kinase catalyses the interconversion of adenosine phosphates, and plays a crucial role in maintaining cellular energy homeostasis. Here, the authors use single molecule optical tweezers to understand how the enzyme’s conformation dynamics modulates catalysis.

    • Benjamin Pelz
    • , Gabriel Žoldák
    •  & Matthias Rief

  • Article
    | Open Access

    The tumor suppressor BAP1 is activated by ASXL1 to deubiquitinate mono-ubiquitinated H2A at K119 in Polycomb gene repression. Here, the authors show how BAP1’s C-terminal extension auto-recruits it to nucleosomes, where the DEUBAD domain of ASXL1 increases BAP1’s affinity for ubiquitin to drive deubiquitination.

    • Danny D. Sahtoe
    • , Willem J. van Dijk
    •  & Titia K. Sixma

  • 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

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