Enzyme mechanisms articles within Nature Communications

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  • Article
    | Open Access

    In silico models of cells can provide insight into the causes and effects of disease states and reduce the need for in vivo studies. Here, the authors present a kinetic model of hepatocyte metabolism including energy, carbohydrate, lipid and nitrogen metabolism and hormonal and allosteric regulation of enzymatic activity.

    • Nikolaus Berndt
    • , Sascha Bulik
    •  & Hermann-Georg Holzhütter

  • Article
    | Open Access

    Thioplatensimycin (thioPTM) and thioplatencin (thioPTN) are recently discovered thiocarboxylic acid congeners of the antibacterial compounds PTM and PTN. Here, the authors identify a thioacid cassette encoding PtmA3 and PtmU4 that are responsible for carboxylate activation and sulfur transfer, respectively.

    • Liao-Bin Dong
    • , Jeffrey D. Rudolf
    •  & Ben Shen

  • Article
    | Open Access

    Proteasomal ATPases contain functionally important coiled-coil (CC) domains, the mechanistic role of which is not fully understood. Here, the authors provide evidence for three distinct CC conformations, showing that CC conformational changes enable ATPases to switch between active and resting states.

    • Aaron Snoberger
    • , Evan J. Brettrager
    •  & David M. Smith

  • Article
    | Open Access

    The enzymes Rif15 and Rif16 are involved in the late steps of the biosynthesis of rifamycins, a group of antibiotics. Here, the authors characterized these two proteins and found that they catalyse unusual biochemical reactions.

    • Feifei Qi
    • , Chao Lei
    •  & Shengying Li

  • Article
    | Open Access

    The bacterial protein disaggregation machine ClpB uses ATP to generate mechanical force to unfold and thread its protein substrates. Here authors visualize the ClpB ring using high-speed atomic force microscopy and capture conformational changes of the hexameric ring during the ATPase reaction.

    • Takayuki Uchihashi
    • , Yo-hei Watanabe
    •  & Toshio Ando

  • Article
    | Open Access

    Toxin–antitoxin (TA) systems are important modulators of bacterial physiology. Here, the authors structurally characterize the epsilon/zeta TA system from the Gram-negative pathogen Neisseria gonorrhoeae and show that the toxin interferes with peptidoglycan and lipopolysaccharide synthesis by phosphorylating the UDP-activated sugar-precursors.

    • Andrea Rocker
    • , Madeleine Peschke
    •  & Anton Meinhart

  • Article
    | Open Access

    The bacterial transcription-repair coupling factor Mfd displaces stalled RNA polymerase (RNAP) by promoting transcription termination at sites of DNA lesions. Here the authors find—using single molecule imaging in live Escherichia coli—that RNAP stalls frequently during transcription, and needs to be rescued by Mfd during normal growth.

    • Han N. Ho
    • , Antoine M. van Oijen
    •  & Harshad Ghodke

  • Article
    | Open Access

    Ubiquitylation of H2B is associated with transcription and regulation of chromatin structure. Here, the authors perform an unbiased screen to identify the role of chromatin modifications on ubiquitylation of H2BK120 and characterize the crosstalk between H2BK120ub and H2A modifications and variants.

    • Felix Wojcik
    • , Geoffrey P. Dann
    •  & Tom W. Muir

  • Article
    | Open Access

    Carrier domain enzymes accomplish catalysis by physically transporting intermediates long distances between remote active sites. Here the authors describe a wide range of catalytically productive translocation events during catalysis by pyruvate carboxylase and suggest a basis for its allosteric activation.

    • Yumeng Liu
    • , Melissa M. Budelier
    •  & Martin St. Maurice

  • Article
    | Open Access

    Jumonji-C domain containing protein 5 (JMJD5) is essential for animal development but its catalytic activity has remained elusive so far. Here the authors show that human JMJD5 is an arginyl-hydroxylase and present the cofactor, substrate and product bound JMJD5 crystal structures.

    • Sarah E. Wilkins
    • , Md. Saiful Islam
    •  & Rasheduzzaman Chowdhury

  • Article
    | Open Access

    The catalytic activity of dioxygenase AsqJ is strictly relying on the methylation of quinolone substrates. Here, the authors apply molecular simulations, X-ray crystallography and in vitro biochemical studies to the engineering of dioxygenase AsqJ with improved catalytic activity for modified non-methylated surrogates.

    • Sophie L. Mader
    • , Alois Bräuer
    •  & Ville R. I. Kaila

  • Article
    | Open Access

    Disruption of the ubiquitin proteasome system (UPS) is often associated with neurodegenerative diseases. Here the authors demonstrate the existence of a general mechanism of proteasomal impairment triggered by a specific protein oligomer structure, irrespective of its protein constituent.

    • Tiffany A. Thibaudeau
    • , Raymond T. Anderson
    •  & David M. Smith

  • Article
    | Open Access

    Poly(ADP-ribose) polymerases (PARPs) catalyse ADP-ribose posttranslational modifications using NAD+ as a substrate. Here, the authors present the crystal structure of PARP-1 bound to the non-hydrolyzable NAD+ analog BAD and provide insights into the mechanism of PARP-1 allosteric regulation.

    • Marie-France Langelier
    • , Levani Zandarashvili
    •  & John M. Pascal

  • Article
    | Open Access

    Deubiquitinating enzymes (DUBs) are essential to modulate ubiquitin signaling. While known DUBs can be grouped into six families, the authors here present biochemical and structural evidence for a seventh DUB family, defining determinants of substrate specificity for two representative enzymes.

    • Thomas Hermanns
    • , Christian Pichlo
    •  & Kay Hofmann

  • Article
    | Open Access

    Calcium-independent phospholipase A2β (iPLA2β) is involved in many physiological and pathological processes but the underlying mechanisms are largely unknown. Here, the authors present the structure of dimeric iPLA2β, providing insights into the regulation of its activity and cellular localization.

    • Konstantin R. Malley
    • , Olga Koroleva
    •  & Sergey Korolev

  • Article
    | Open Access

    The number of tRNA isodecoders has expanded significantly during evolution, which has resulted in ambiguity in tRNA selection by synthetases. Here the authors identify and characterize a dedicated proofreading factor that eliminates errors caused by ambiguity in tRNA selection by eukaryotic tRNA synthetases.

    • Santosh Kumar Kuncha
    • , Mohd Mazeed
    •  & Rajan Sankaranarayanan

  • Article
    | Open Access

    UPF1 is a central protein in nonsense-mediated mRNA decay (NMD), but contribution of its RNA processivity to NMD is unclear. Here, the authors show how the retroviral Tax protein interacts with and inhibits UPF1, and demonstrate that UPF1’s translocase activity contributes to NMD.

    • Francesca Fiorini
    • , Jean-Philippe Robin
    •  & Vincent Mocquet

  • Article
    | Open Access

    Metallo-β-lactamases (MBL) are zinc containing enzymes that cause resistance to β-lactam antibiotics. Here the authors show that the anti-Helicobacter pylori drug colloidal bismuth subcitrate inhibits MBLs by displacing the zinc ions with Bi(III), which is of great interest for the development of antibiotics.

    • Runming Wang
    • , Tsz-Pui Lai
    •  & Hongzhe Sun

  • Article
    | Open Access

    Poly(ethylene terephthalate) (PET) is a widely used plastic and its accumulation in the environment has become global problem. Here the authors report the crystal structure of a Ideonella sakaiensis PET-degrading enzyme and propose a molecular mechanism for PET degradation.

    • Seongjoon Joo
    • , In Jin Cho
    •  & Kyung-Jin Kim

  • Article
    | Open Access

    The essential DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) has both endonuclease and exonuclease activities. Here, the authors present DNA bound human APE1 crystal structures which give insights into its exonuclease mechanism.

    • Amy M. Whitaker
    • , Tony S. Flynn
    •  & Bret D. Freudenthal

  • Article
    | Open Access

    The mechanism for covalent flavinylation of flavoenzymes is still unclear. Here, the authors propose a mechanism based on the crystal structure of a flavinylation assembly intermediate of the E. coli respiratory Complex II comprising the E. coli FrdA subunit bound to covalent FAD and crosslinked with its assembly factor SdhE.

    • Pankaj Sharma
    • , Elena Maklashina
    •  & T. M. Iverson

  • Article
    | Open Access

    Lysosomal degradation of sphingolipids requires lipid-binding saposin proteins and hydrolytic enzymes. Here the authors present the crystal structure of the hydrolase β-galactocerebrosidase in complex with saposin SapA and give insights into the glycosphingolipid galactocerebroside degradation mechanism.

    • Chris H. Hill
    • , Georgia M. Cook
    •  & Janet E. Deane

  • Article
    | Open Access

    Pex1 and Pex6 form a heterohexameric Type-2 AAA-ATPase motor whose function in peroxisomal matrix-protein import is still debated. Here, the authors combine structural, biochemical, and cell-biological approaches to show that Pex1/Pex6 is a protein unfoldase, which supports a role in mechanical unfolding of peroxin proteins.

    • Brooke M. Gardner
    • , Dominic T. Castanzo
    •  & Andreas Martin

  • Article
    | Open Access

    Non-heme iron and α-ketoglutarate (αKG) oxygenases play a major role in fungal meroterpenoid biosynthesis, but their mechanism remains elusive. Here the authors present crystal structures of two oxygenases, AusE and PrhA, which provide insights into the multifunctional nature of these enzymes.

    • Yu Nakashima
    • , Takahiro Mori
    •  & Ikuro Abe

  • Article
    | Open Access

    H+-ATPases employ a rotary catalytic mechanism to couple ATP synthesis/hydrolysis with proton translocation through the membrane. Here, the authors use high-resolution cryoEM to characterize three rotational states of a bacterial H+-ATPase, providing a more detailed model of its catalytic mechanism.

    • Atsuko Nakanishi
    • , Jun-ichi Kishikawa
    •  & Ken Yokoyama

  • Article
    | Open Access

    The mitochondrial RNA degradosome (mtEXO) plays an essential role in the regulation of mitochondrial gene expression and is composed of the 3′-to-5′ exoribonuclease Dss1 and the helicase Suv3. Here the authors present the RNA bound mtEXO crystal structure and give insights into its mechanism.

    • Michal Razew
    • , Zbigniew Warkocki
    •  & Marcin Nowotny

  • Article
    | Open Access

    Protein phosphatase 2A (PP2A) forms different holoenzymes but little is known about the disassembly of these important signalling complexes. Here the authors present the crystal structure of PP2A bound to TOR signaling pathway regulator (TIPRL) and give insights into the methylation-dependent disassembly of PP2A holenzymes.

    • Cheng-Guo Wu
    • , Aiping Zheng
    •  & Yongna Xing

  • Article
    | Open Access

    An understanding of the dynamics of drug binding and unbinding processes is important for drug discovery. Here, the authors give insights into the binding mechanism of small drug-like molecules to human Hsp90 by combining thermodynamics and kinetics studies as well as molecular dynamics simulations.

    • M. Amaral
    • , D. B. Kokh
    •  & M. Frech

  • Article
    | Open Access

    New Delhi metallo-β-lactamases (NDMs) hydrolyze almost all β-lactam antibiotics and pose a major public health threat. Here, the authors study the mechanism of NDM-1 catalyzed carbapenem hydrolysis and present the crystal structures of the enzyme-intermediate and product complexes, which is important for drug design.

    • Han Feng
    • , Xuehui Liu
    •  & Wei Liu

  • Article
    | Open Access

    A subset of α/β hydrolases is known to suppress the pathogen-triggered hypersensitive response (HR) in plants, but their mechanism of action remains unclear. The authors present two crystal structures and functional analyses of these enzymes, showing that HR is suppressed by a previously unknown family of deacetylases.

    • Marco Bürger
    • , Björn C. Willige
    •  & Joanne Chory

  • Article
    | Open Access

    Poly-ethylene terephthalate (PET) is a widely used plastic which accumulates in the environment with detrimental consequences. Here the authors report crystal structures of a PET-hydrolyzing enzyme from the microbe Ideonella sakaiensis bound to substrate and product analogs, and suggest a catalytic mechanism for its PET-degrading activity.

    • Xu Han
    • , Weidong Liu
    •  & Rey-Ting Guo

  • Article
    | Open Access

    RNA-cleaving DNA enzymes are catalytic DNA that can cleave RNA in a sequence-specific manner. Here, the authors report three crystal structures of the 8–17 DNAzyme that include the pre-catalytic state of the RNA cleavage reaction, providing insight into the catalytic mechanism and may guide the rational design of DNAzymes.

    • Hehua Liu
    • , Xiang Yu
    •  & Jianhua Gan

  • Article
    | Open Access

    Pyruvate kinase (PYK) controls glycolytic flux. Here, the authors combine biochemical, structural and computational modelling studies to characterize the allosteric mechanisms regulating Mycobacterium tuberculosis PYK activity and show that AMP and glucose-6-phosphate are synergistic allosteric activators of the enzyme.

    • Wenhe Zhong
    • , Liang Cui
    •  & Peter C. Dedon

  • Article
    | Open Access

    The spindle checkpoint ensures the fidelity of chromosome segregation during mitosis and meiosis. Here the authors use a combination of biochemical and structural biology approaches to show how the TRIP13 ATPase and its adaptor, p31comet, catalyze the conversion of the checkpoint protein Mad2 between latent and active forms

    • Melissa L. Brulotte
    • , Byung-Cheon Jeong
    •  & Xuelian Luo

  • Article
    | Open Access

    GalNAc transferases’ (GalNAc-Ts) catalytic domains are connected to a lectin domain through a flexible linker. Here the authors present a structural analysis of GalNAc-T4 that implicates the linker region as modulator of the orientations of the lectin domain, which in turn imparts substrate specificity.

    • Matilde de las Rivas
    • , Erandi Lira-Navarrete
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    Transcript cleavage factors such as eukaryotic TFIIS assist the resumption of transcription following RNA pol II backtracking. Here the authors find that one of the Sulfolobus solfataricus TFIIS homolog—TFS4—has evolved into a potent RNA polymerase inhibitor potentially involved in antiviral defense.

    • Thomas Fouqueau
    • , Fabian Blombach
    •  & Finn Werner

  • Article
    | Open Access

    TRAF6 is a RING E3 ligase that builds Lys63-linked ubiquitin chains. Here, the authors present the crystal structure of TRAF6 bound to the Ubc13~Ub conjugate, which, together with biochemical assays, reveals the role of the zinc finger domains and why RING dimerisation is required for TRAF6 activity.

    • Adam J. Middleton
    • , Rhesa Budhidarmo
    •  & Catherine L. Day

  • Article
    | Open Access

    Primase is the specialised DNA-dependent RNA polymerase responsible for the initiation of DNA synthesis during DNA replication. Here the authors use a structural biology approach to identify the initiation site in the S. solfataricus PriSLX primase and to demonstrate that its Fe-S cluster is dispensable for primer synthesis.

    • Sandro Holzer
    • , Jiangyu Yan
    •  & Luca Pellegrini

  • Article
    | Open Access

    Drosha and DGCR8 constitute the core Microprocessor complex, which processes primary microRNAs (pri-miRs) into mature microRNAs. Here the authors show that heme is essential for the proper processing of pri-miRs by Drosha-DGCR8, and the molecular mechanism by which heme enhances processing fidelity.

    • Alexander C. Partin
    • , Tri D. Ngo
    •  & Yunsun Nam

  • Article
    | Open Access

    Using photosensitive caged-compound for femtosecond crystallography at X-ray free electron lasers would allow the structure determination of reaction intermediates. Here the authors demonstrate the feasibility of this approach with a caged NO-compound and present the initial NO-bound intermediate structure of cytochrome P450 nitric oxide reductase.

    • Takehiko Tosha
    • , Takashi Nomura
    •  & Minoru Kubo

  • Article
    | Open Access

    The electron-transferring flavoprotein / butyryl-CoA dehydrogenase (EtfAB/Bcd) complex catalyzes the reduction of crotonyl-CoA and ferredoxins by NADH in anaerobic microbes. Here, the authors present the crystal structure of Clostridium difficile EtfAB/Bcd and discuss the bifurcation mechanism for electron flow.

    • Julius K. Demmer
    • , Nilanjan Pal Chowdhury
    •  & Wolfgang Buckel

  • Article
    | Open Access

    The catalytic subunit E9 of the vaccinia virus DNA polymerase forms a functional polymerase holoenzyme by interacting with the heterodimeric processivity factor A20/D4. Here the authors present the structure of full-length E9 and show that an insertion within its palm domain binds A20, in a mode different from other family B polymerases.

    • Nicolas Tarbouriech
    • , Corinne Ducournau
    •  & Frédéric Iseni

  • Article
    | Open Access

    CRISPR-Cas9 is widely used for genome engineering but structural data for the DNA cleavage step are still incomplete. Here, the authors present the cryo-EM structure of a ternary Cas9-sgRNA-target DNA complex, perform MD simulations and discuss implications for the Cas9 DNA cleavage mechanism.

    • Cong Huai
    • , Gan Li
    •  & Qiang Huang

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