当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > Mechanism-Based Post-Translational Modification and Inactivation in Terpene Synthases.

Mechanism-Based Post-Translational Modification and Inactivation in Terpene Synthases.

Abstract：

:Terpenes are ubiquitous natural chemicals with diverse biological functions spanning all three domains of life. In specialized metabolism, the active sites of terpene synthases (TPSs) evolve in shape and reactivity to direct the biosynthesis of a myriad of chemotypes for organismal fitness. As most terpene biosynthesis mechanistically involves highly reactive carbocationic intermediates, the protein surfaces catalyzing these cascade reactions possess reactive regions possibly prone to premature carbocation capture and potentially enzyme inactivation. Here, we show using proteomic and X-ray crystallographic analyses that cationic intermediates undergo capture by conserved active site residues leading to inhibitory self-alkylation. Moreover, the level of cation-mediated inactivation increases with mutation of the active site, upon changes in the size and structure of isoprenoid diphosphate substrates, and alongside increases in reaction temperatures. TPSs that individually synthesize multiple products are less prone to self-alkylation then TPSs possessing relatively high product specificity. In total, the results presented suggest that mechanism-based alkylation represents an overlooked mechanistic pressure during the evolution of cation-derived terpene biosynthesis.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Kersten RD,Diedrich JK,Yates JR 3rd,Noel JP

doi

10.1021/acschembio.5b00539

subject

Has Abstract

pub_date

2015-11-20 00:00:00

pages

2501-11

issue

11

eissn

1554-8929

issn

1554-8937

journal_volume

10

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • The Recognition of Unrelated Ligands by Identical Proteins.

    abstract：:Unrelated ligands, often found in drug discovery campaigns, can bind to the same receptor, even with the same protein residues. To investigate how this might occur, and whether it might be typically possible to find unrelated ligands for the same drug target, we sought examples of topologically unrelated ligands that ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00443

    authors： Pottel J,Levit A,Korczynska M,Fischer M,Shoichet BK

    更新日期：2018-09-21 00:00:00

  • Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader.

    abstract：:SGK3 is a PX domain containing protein kinase activated at endosomes downstream of class 1 and 3 PI3K family members by growth factors and oncogenic mutations. SGK3 plays a key role in mediating resistance of breast cancer cells to class 1 PI3K or Akt inhibitors, by substituting for the loss of Akt activity and restor...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00505

    authors： Tovell H,Testa A,Zhou H,Shpiro N,Crafter C,Ciulli A,Alessi DR

    更新日期：2019-09-20 00:00:00

  • CXC-Mediated Cellular Uptake of Miniproteins: Forsaking "Arginine Magic".

    abstract：:Miniproteins have a size between that of larger biologics and small molecules and presumably possess the advantages of both; they represent an expanding class of promising scaffolds for the design of affinity reagents, enzymes, and therapeutics. Conventional strategies to promote cellular uptake of miniproteins rely o...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00564

    authors： Meng X,Li T,Zhao Y,Wu C

    更新日期：2018-11-16 00:00:00

  • Inhibition of DC-SIGN-mediated HIV infection by a linear trimannoside mimic in a tetravalent presentation.

    abstract：:HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this context, dendritic cell-specific ICAM-3 grabbing non-inte...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900216e

    authors： Sattin S,Daghetti A,Thépaut M,Berzi A,Sánchez-Navarro M,Tabarani G,Rojo J,Fieschi F,Clerici M,Bernardi A

    更新日期：2010-03-19 00:00:00

  • Novel modifications in RNA.

    abstract：:The past several years have seen numerous reports of new chemical modifications for use in RNA. In addition, in that time period, we have seen the discovery of several previously unknown naturally occurring modifications that impart novel properties on the parent RNAs. In this review, we describe recent discoveries in...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb200422t

    authors： Phelps K,Morris A,Beal PA

    更新日期：2012-01-20 00:00:00

  • Generation of Optogenetically Modified Adenovirus Vector for Spatiotemporally Controllable Gene Therapy.

    abstract：:Gene therapy is expected to be utilized for the treatment of various diseases. However, the spatiotemporal resolution of current gene therapy technology is not high enough. In this study, we generated a new technology for spatiotemporally controllable gene therapy. We introduced optogenetic and CRISPR/Cas9 techniques ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b01058

    authors： Takayama K,Mizuguchi H

    更新日期：2018-02-16 00:00:00

  • Rational design of an auxin antagonist of the SCF(TIR1) auxin receptor complex.

    abstract：:The plant hormone auxin is a master regulator of plant growth and development. By regulating rates of cell division and elongation and triggering specific patterning events, indole 3-acetic acid (IAA) regulates almost every aspect of plant development. The perception of auxin involves the formation of a ternary comple...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200404c

    authors： Hayashi K,Neve J,Hirose M,Kuboki A,Shimada Y,Kepinski S,Nozaki H

    更新日期：2012-03-16 00:00:00

  • Peptides derived from the transmembrane domain of Bcl-2 proteins as potential mitochondrial priming tools.

    abstract：:The Bcl-2 family of proteins is crucial for apoptosis regulation. Members of this family insert through a specific C-terminal anchoring transmembrane domain (TMD) in the mitochondrial outer membrane where they hierarchically interact to determine cell fate. While the mitochondrial membrane has been proposed to activel...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb5002679

    authors： Andreu-Fernández V,Genoves A,Lee TH,Stellato M,Lucantoni F,Orzáez M,Mingarro I,Aguilar MI,Pérez-Payá E

    更新日期：2014-08-15 00:00:00

  • Using a Specific RNA-Protein Interaction To Quench the Fluorescent RNA Spinach.

    abstract：:RNAs are involved in interaction networks with other biomolecules and are crucial for proper cell function. Yet their biochemical analysis remains challenging. For Förster Resonance Energy Transfer (FRET), a common tool to study such interaction networks, two interacting molecules have to be fluorescently labeled. "Sp...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00332

    authors： Roszyk L,Kollenda S,Hennig S

    更新日期：2017-12-15 00:00:00

  • Biochemical and biophysical analysis of a chiral PqsD inhibitor revealing tight-binding behavior and enantiomers with contrary thermodynamic signatures.

    abstract：:Antivirulence strategies addressing bacterial pathogenicity without exhibiting growth inhibition effects represent a novel approach to overcome today's crisis in antibiotic development. In recent studies, we examined various inhibitors of PqsD, an enzyme involved in formation of Pseudomonas aeruginosa cell-to-cell sig...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400530d

    authors： Storz MP,Brengel C,Weidel E,Hoffmann M,Hollemeyer K,Steinbach A,Müller R,Empting M,Hartmann RW

    更新日期：2013-12-20 00:00:00

  • Structural analysis of the contacts anchoring moenomycin to peptidoglycan glycosyltransferases and implications for antibiotic design.

    abstract：:Peptidoglycan glycosyltransferases (PGTs), enzymes that catalyze the formation of the glycan chains of the bacterial cell wall, have tremendous potential as antibiotic targets. The moenomycins, a potent family of natural product antibiotics, are the only known active site inhibitors of the PGTs and serve as blueprints...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb800078a

    authors： Yuan Y,Fuse S,Ostash B,Sliz P,Kahne D,Walker S

    更新日期：2008-07-18 00:00:00

  • Calcium-dependent ligand binding and G-protein signaling of family B GPCR parathyroid hormone 1 receptor purified in nanodiscs.

    abstract：:GPCRs mediate intracellular signaling upon external stimuli, making them ideal drug targets. However, little is known about their activation mechanisms due to the difficulty in purification. Here, we introduce a method to purify GPCRs in nanodiscs, which incorporates GPCRs into lipid bilayers immediately after membran...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300466n

    authors： Mitra N,Liu Y,Liu J,Serebryany E,Mooney V,DeVree BT,Sunahara RK,Yan EC

    更新日期：2013-03-15 00:00:00

  • Reprogramming a Deubiquitinase into a Transamidase.

    abstract：:Access to well-defined ubiquitin conjugates has been key to elucidating the biochemical functions of proteins in the ubiquitin signaling network. Yet, we have a poor understanding of how deubiquitinases and ubiquitin-binding proteins respond to ubiquitin modifications when anchored to a protein other than ubiquitin or...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00759

    authors： Chang LH,Strieter ER

    更新日期：2018-09-21 00:00:00

  • Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism.

    abstract：:In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into toxic assemblies causing islet β-cell death. Therefore, preventing IAPP toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01 is a supramolecular tool for selective complexation of K residues in (poly)peptides. ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00146

    authors： Lopes DH,Attar A,Nair G,Hayden EY,Du Z,McDaniel K,Dutt S,Bravo-Rodriguez K,Mittal S,Klärner FG,Wang C,Sanchez-Garcia E,Schrader T,Bitan G

    更新日期：2015-06-19 00:00:00

  • Botryllamides: natural product inhibitors of ABCG2.

    abstract：:ABCG2 is a membrane-localized, human transporter protein that has been demonstrated to reduce the intracellular accumulation of substrates through ATP-dependent efflux. Highly expressed in placental syncytiotrophoblasts, brain microvasculature, and the gastrointestinal tract, ABCG2 has been shown to mediate normal tis...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900134c

    authors： Henrich CJ,Robey RW,Takada K,Bokesch HR,Bates SE,Shukla S,Ambudkar SV,McMahon JB,Gustafson KR

    更新日期：2009-08-21 00:00:00

  • Multiple Chemical Inducible Tal Effectors for Genome Editing and Transcription Activation.

    abstract：:Inducible modulation is often required for precise investigations and manipulations of dynamic biological processes. Transcription activator-like effectors (TALEs) provide a powerful tool for targeted gene editing and transcriptional programming. We designed a series of chemical inducible systems by coupling TALEs wit...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00606

    authors： Zhao C,Zhang Y,Zhao Y,Ying Y,Ai R,Zhang J,Wang Y

    更新日期：2018-03-16 00:00:00

  • Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners.

    abstract：:Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 acti...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300108c

    authors： Pollock JA,Larrea MD,Jasper JS,McDonnell DP,McCafferty DG

    更新日期：2012-07-20 00:00:00

  • Structure and cell wall cleavage by modular lytic transglycosylase MltC of Escherichia coli.

    abstract：:The lytic transglycosylases are essential bacterial enzymes that catalyze the nonhydrolytic cleavage of the glycan strands of the bacterial cell wall. We describe here the structural and catalytic properties of MltC, one of the seven lytic transglycosylases found in the genome of the Gram-negative bacterium Escherichi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500439c

    authors： Artola-Recolons C,Lee M,Bernardo-García N,Blázquez B,Hesek D,Bartual SG,Mahasenan KV,Lastochkin E,Pi H,Boggess B,Meindl K,Usón I,Fisher JF,Mobashery S,Hermoso JA

    更新日期：2014-09-19 00:00:00

  • Reaction mechanism of N-acetylneuraminic acid lyase revealed by a combination of crystallography, QM/MM simulation, and mutagenesis.

    abstract：:N-Acetylneuraminic acid lyase (NAL) is a Class I aldolase that catalyzes the reversible condensation of pyruvate with N-acetyl-d-mannosamine (ManNAc) to yield the sialic acid N-acetylneuraminic acid (Neu5Ac). Aldolases are finding increasing use as biocatalysts for the stereospecific synthesis of complex molecules. In...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500067z

    authors： Daniels AD,Campeotto I,van der Kamp MW,Bolt AH,Trinh CH,Phillips SE,Pearson AR,Nelson A,Mulholland AJ,Berry A

    更新日期：2014-04-18 00:00:00

  • Probing enzymes late in the trypanosomal glycosylphosphatidylinositol biosynthetic pathway with synthetic glycosylphosphatidylinositol analogues.

    abstract：:Glycosylphosphatidylinositol (GPI)-anchored proteins are abundant in the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness in humans and the related disease Nagana in cattle, and disruption of GPI biosynthesis is genetically and chemically validated as a drug target. Here, we exam...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb800143w

    authors： Urbaniak MD,Yashunsky DV,Crossman A,Nikolaev AV,Ferguson MA

    更新日期：2008-10-17 00:00:00

  • Bacterial Riboswitches and Ribozymes Potently Activate the Human Innate Immune Sensor PKR.

    abstract：:The innate immune system provides the first line of defense against pathogens through the recognition of nonspecific patterns in RNA to protect the cell in a generalized way. The human RNA-activated protein kinase, PKR, is a dsRNA binding protein and an essential sensor in the innate immune response, which recognizes ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00081

    authors： Hull CM,Anmangandla A,Bevilacqua PC

    更新日期：2016-04-15 00:00:00

  • Advances in the Chemical Biology of Desferrioxamine B.

    abstract：:Desferrioxamine B (DFOB) was discovered in the late 1950s as a hydroxamic acid metabolite of the soil bacterium Streptomyces pilosus. The exquisite affinity of DFOB for Fe(III) identified its potential for removing excess iron from patients with transfusion-dependent hemoglobin disorders. Many studies have used semisy...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/acschembio.7b00851

    authors： Codd R,Richardson-Sanchez T,Telfer TJ,Gotsbacher MP

    更新日期：2018-01-19 00:00:00

  • Cytosolic Delivery of Macromolecules in Live Human Cells Using the Combined Endosomal Escape Activities of a Small Molecule and Cell Penetrating Peptides.

    abstract：:Ineffective cellular delivery is a common problem in numerous biological applications. Developing delivery reagents that work robustly in a variety of experimental settings remains a challenge. Herein, we report how peptides derived from the prototypical cell penetrating peptide TAT can be used in combination with a s...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00585

    authors： Allen J,Najjar K,Erazo-Oliveras A,Kondow-McConaghy HM,Brock DJ,Graham K,Hager EC,Marschall ALJ,Dübel S,Juliano RL,Pellois JP

    更新日期：2019-12-20 00:00:00

  • The Supersized Class III Lanthipeptide Stackepeptin Displays Motif Multiplication in the Core Peptide.

    abstract：:Lanthipeptides are ribosomally synthesized and post-translationally modified peptides bearing the characteristic amino acids lanthionine and/or labionin. Here, we report on the discovery and characterization of the stackepeptins, produced by the Actinomycete Stackebrandtia nassauensis DSM-44728(T). The stackepeptins a...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00651

    authors： Jungmann NA,van Herwerden EF,Hügelland M,Süssmuth RD

    更新日期：2016-01-15 00:00:00

  • Repair of Alkylation Damage in Eukaryotic Chromatin Depends on Searching Ability of Alkyladenine DNA Glycosylase.

    abstract：:Human alkyladenine DNA glycosylase (AAG) initiates the base excision repair pathway by excising alkylated and deaminated purine lesions. In vitro biochemical experiments demonstrate that AAG uses facilitated diffusion to efficiently search DNA to find rare sites of damage and suggest that electrostatic interactions ar...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00409

    authors： Zhang Y,O'Brien PJ

    更新日期：2015-11-20 00:00:00

  • Biocatalytic Detoxification of Paralytic Shellfish Toxins.

    abstract：:Small molecules that bind to voltage-gated sodium channels (VGSCs) are promising leads in the treatment of numerous neurodegenerative diseases and pain. Nature is a highly skilled medicinal chemist in this regard, designing potent VGSC ligands capable of binding to and blocking the channel, thereby offering compounds ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00123

    authors： Lukowski AL,Denomme N,Hinze ME,Hall S,Isom LL,Narayan ARH

    更新日期：2019-05-17 00:00:00

  • Reporter enzyme inhibitor study to aid assembly of orthogonal reporter gene assays.

    abstract：:Reporter gene assays (RGAs) are commonly used to measure biological pathway modulation by small molecules. Understanding how such compounds interact with the reporter enzyme is critical to accurately interpret RGA results. To improve our understanding of reporter enzymes and to develop optimal RGA systems, we investig...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb3007264

    authors： Ho PI,Yue K,Pandey P,Breault L,Harbinski F,McBride AJ,Webb B,Narahari J,Karassina N,Wood KV,Hill A,Auld DS

    更新日期：2013-05-17 00:00:00

  • Molecular Networking and Whole-Genome Analysis Aid Discovery of an Angucycline That Inactivates mTORC1/C2 and Induces Programmed Cell Death.

    abstract：:Rediscovery of known compounds and time consumed in identification, especially high molecular weight compounds with complex structure, have let down interest in drug discovery. In this study, whole-genome analysis of microbe and Global Natural Products Social (GNPS) molecular networking helped in initial understanding...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00026

    authors： Dan VM,J S V,C J S,Sanawar R,Lekshmi A,Kumar RA,Santhosh Kumar TR,Marelli UK,Dastager SG,Pillai MR

    更新日期：2020-03-20 00:00:00

  • Enzymatic Plasticity Inspired by the Diterpene Cyclase CotB2.

    abstract：:Enzymatic plasticity, as a modern term referring to the functional conversion of an enzyme, is significant for enzymatic activity redesign. The bacterial diterpene cyclase CotB2 is a typical plastic enzyme by which its native form precisely conducts a chemical reaction while its mutants diversify the catalytic functio...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00645

    authors： Tang X,Zhang F,Zeng T,Li W,Yin S,Wu R

    更新日期：2020-10-16 00:00:00

  • Cell Permeable Ratiometric Fluorescent Sensors for Imaging Phosphoinositides.

    abstract：:Phosphoinositides are critical cell-signal mediators present on the plasma membrane. The dynamic change of phosphoinositide concentrations on the membrane including clustering and declustering mediates signal transduction. The importance of phosphoinositides is scored by the fact that they participate in almost all ce...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00067

    authors： Mondal S,Rakshit A,Pal S,Datta A

    更新日期：2016-07-15 00:00:00