当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > Characterization of Class IB Terpene Synthase: The First Crystal Structure Bound with a Substrate Surrogate.

Characterization of Class IB Terpene Synthase: The First Crystal Structure Bound with a Substrate Surrogate.

Abstract：

:Terpene synthases (TS) are classified into two broad types, Class I and II, based on the chemical strategy for initial carbocation formation and motif sequences of the catalytic site. We have recently identified a new class of enzymes, Class IB, showing the acceptability of long (C20-C35) prenyl-diphosphates as substrates and no amino acid sequence homology with known TS. Conversion of long prenyl-diphosphates such as heptaprenyl-diphosphate (C35) is unusual and has never been reported for Class I and II enzymes. Therefore, the characterization of Class IB enzymes is crucial to understand the reaction mechanism of the extensive terpene synthesis. Here, we report the crystal structure bound with a substrate surrogate and biochemical analysis of a Class IB TS, using the enzyme from Bacillus alcalophilus (BalTS). The structure analysis revealed that the diphosphate part of the substrate is located around the two characteristic Asp-rich motifs, and the hydrophobic tail is accommodated in a unique hydrophobic long tunnel, where the C35 prenyl-diphosphate, the longest substrate of BalTS, can be accepted. Biochemical analyses of BalTS showed that the enzymatic property, such as Mg2+ dependency, is similar to those of Class I enzymes. In addition, a new cyclic terpene was identified from BalTS reaction products. Mutational analysis revealed that five of the six Asp residues in the Asp-rich motifs and two His residues are essential for the formation of the cyclic skeleton. These results provided a clue to consider the application of the unusual large terpene synthesis by Class IB enzymes.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Stepanova R,Inagi H,Sugawara K,Asada K,Nishi T,Ueda D,Yasuno Y,Shinada T,Miki K,Fujihashi M,Sato T

doi

10.1021/acschembio.0c00145

subject

Has Abstract

pub_date

2020-06-19 00:00:00

pages

1517-1525

issue

6

eissn

1554-8929

issn

1554-8937

journal_volume

15

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • Functional evaluation of key interactions evident in the structure of the eukaryotic Cys-loop receptor GluCl.

    abstract：:The publication of the first high-resolution crystal structure of a eukaryotic Cys-loop receptor, GluClα, has provided valuable structural information on this important class of ligand-gated ion channels (LGIC). However, limited functional data exist for the GluCl receptors. Before applying the structural insights fro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500323d

    authors： Daeffler KN,Lester HA,Dougherty DA

    更新日期：2014-10-17 00:00:00

  • The N-Terminal Domain of NPHP1 Folds into a Monomeric Left-Handed Antiparallel Three-Stranded Coiled Coil with Anti-apoptotic Function.

    abstract：:Mutations in the NPHP1 gene, coding for human nephrocystin-1 (NPHP1), cause the autosomal recessive disease nephronophthisis, the most common cause of end-stage renal disease in children and adolescents. The function and structure of NPHP1 are still poorly characterized. NPHP1 presents a modular structure well in keep...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00582

    authors： Mannella V,Quilici G,Nigro EA,Lampis M,Minici C,Degano M,Boletta A,Musco G

    更新日期：2019-08-16 00:00:00

  • Parsimonious discovery of synergistic drug combinations.

    abstract：:Combination therapies that enhance efficacy or permit reduced dosages to be administered have seen great success in a variety of therapeutic applications. More fundamentally, the discovery of epistatic pathway interactions not only informs pharmacologic intervention but can be used to better understand the underlying ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb2003225

    authors： Severyn B,Liehr RA,Wolicki A,Nguyen KH,Hudak EM,Ferrer M,Caldwell JS,Hermes JD,Li J,Tudor M

    更新日期：2011-12-16 00:00:00

  • pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo.

    abstract：:We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE p...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500388m

    authors： Karabadzhak AG,An M,Yao L,Langenbacher R,Moshnikova A,Adochite RC,Andreev OA,Reshetnyak YK,Engelman DM

    更新日期：2014-11-21 00:00:00

  • Structural Studies Revealed Active Site Distortions of Human Furin by a Small Molecule Inhibitor.

    abstract：:Proprotein convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of several pathologies including cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Here, we present the fi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b01110

    authors： Dahms SO,Jiao GS,Than ME

    更新日期：2017-05-19 00:00:00

  • Revealing coupling patterns in isoprenoid alkylation biocatalysis.

    abstract：:Diversity of scaffold structure and function is a hallmark of the >50,000 isoprenoid natural products such as taxol. Whereas most members of this class are assembled by iterative head-to-tail enzymatic joining reactions between delta2- and delta3-isopentenyl diphosphate (IPP) monomers, dimerization of two delta2-IPP m...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb700094s

    authors： Walsh CT

    更新日期：2007-05-22 00:00:00

  • The Role of Reactive Oxygen Species and Ferroptosis in Heme-Mediated Activation of Human Platelets.

    abstract：:Hemolysis, a process by which the destruction of red blood cells leads to the release of hemoglobin, is a critical event observed during hemolytic disorders. Under oxidative stress conditions, hemoglobin can release its heme prosthetic group, which is highly cytotoxic and can catalyze the generation of reactive oxygen...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00458

    authors： NaveenKumar SK,SharathBabu BN,Hemshekhar M,Kemparaju K,Girish KS,Mugesh G

    更新日期：2018-08-17 00:00:00

  • Evolved sequence contexts for highly efficient amber suppression with noncanonical amino acids.

    abstract：:The expansion of the genetic code with noncanonical amino acids (ncAA) enables the function of proteins to be tailored with high molecular precision. In this approach, the ncAA is charged to an orthogonal nonsense suppressor tRNA by an aminoacyl-tRNA-synthetase (aaRS) and incorporated into the target protein in vivo b...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb5006273

    authors： Pott M,Schmidt MJ,Summerer D

    更新日期：2014-12-19 00:00:00

  • Structural Analysis of the Tobramycin and Gentamicin Clinical Resistome Reveals Limitations for Next-generation Aminoglycoside Design.

    abstract：:Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b01070

    authors： Bassenden AV,Rodionov D,Shi K,Berghuis AM

    更新日期：2016-05-20 00:00:00

  • Steric restrictions of RISC in RNA interference identified with size-expanded RNA nucleobases.

    abstract：:Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modifie...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300174c

    authors： Hernández AR,Peterson LW,Kool ET

    更新日期：2012-08-17 00:00:00

  • Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity.

    abstract：:An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their α-helical conformation, for example, stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb3005403

    authors： Okamoto T,Zobel K,Fedorova A,Quan C,Yang H,Fairbrother WJ,Huang DC,Smith BJ,Deshayes K,Czabotar PE

    更新日期：2013-02-15 00:00:00

  • Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily.

    abstract：:The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the f...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00334

    authors： Wrigley JD,Gavory G,Simpson I,Preston M,Plant H,Bradley J,Goeppert AU,Rozycka E,Davies G,Walsh J,Valentine A,McClelland K,Odrzywol KE,Renshaw J,Boros J,Tart J,Leach L,Nowak T,Ward RA,Harrison T,Andrews DM

    更新日期：2017-12-15 00:00:00

  • Structural and Functional Evidence Indicates Selective Oxygen Signaling in Caldanaerobacter subterraneus H-NOX.

    abstract：:Acute and specific sensing of diatomic gas molecules is an essential facet of biological signaling. Heme nitric oxide/oxygen binding (H-NOX) proteins are a family of gas sensors found in diverse classes of bacteria and eukaryotes. The most commonly characterized bacterial H-NOX domains are from facultative anaerobes a...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00431

    authors： Hespen CW,Bruegger JJ,Phillips-Piro CM,Marletta MA

    更新日期：2016-08-19 00:00:00

  • Crystallographic fragment screening and structure-based optimization yields a new class of influenza endonuclease inhibitors.

    abstract：:Seasonal and pandemic influenza viruses continue to be a leading global health concern. Emerging resistance to the current drugs and the variable efficacy of vaccines underscore the need for developing new flu drugs that will be broadly effective against wild-type and drug-resistant influenza strains. Here, we report ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400400j

    authors： Bauman JD,Patel D,Baker SF,Vijayan RS,Xiang A,Parhi AK,Martínez-Sobrido L,LaVoie EJ,Das K,Arnold E

    更新日期：2013-11-15 00:00:00

  • pH-Dependent DNA Distortion and Repression of Gene Expression by Pectobacterium atrosepticum PecS.

    abstract：:Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene ex...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00168

    authors： Deochand DK,Meariman JK,Grove A

    更新日期：2016-07-15 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

  • Selective tumor cell targeting using low-affinity, multivalent interactions.

    abstract：:This report highlights the advantages of low-affinity, multivalent interactions to recognize one cell type over another. Our goal was to devise a strategy to mediate selective killing of tumor cells, which are often distinguished from normal cells by their higher levels of particular cell surface receptors. To test wh...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb6003788

    authors： Carlson CB,Mowery P,Owen RM,Dykhuizen EC,Kiessling LL

    更新日期：2007-02-20 00:00:00

  • Stable RAGE-heparan sulfate complexes are essential for signal transduction.

    abstract：:RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb4001553

    authors： Xu D,Young JH,Krahn JM,Song D,Corbett KD,Chazin WJ,Pedersen LC,Esko JD

    更新日期：2013-07-19 00:00:00

  • Dark Hydrazone Fluorescence Labeling Agents Enable Imaging of Cellular Aldehydic Load.

    abstract：:Aldehydes are key intermediates in many cellular processes, from endogenous metabolic pathways like glycolysis to undesired exogenously induced processes such as lipid peroxidation and DNA interstrand cross-linking. Alkyl aldehydes are well documented to be cytotoxic, affecting the functions of DNA and protein, and th...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00269

    authors： Yuen LH,Saxena NS,Park HS,Weinberg K,Kool ET

    更新日期：2016-08-19 00:00:00

  • Structure-Based Mutagenesis of Phycobiliprotein smURFP for Optoacoustic Imaging.

    abstract：:Photo- or optoacoustics (OA) imaging is increasingly being used as a non-invasive imaging method that can simultaneously reveal structure and function in deep tissue. However, the most frequent transgenic OA labels are current fluorescent proteins that are not optimized for OA imaging. Thus, they lack OA signal streng...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00299

    authors： Fuenzalida Werner JP,Mishra K,Huang Y,Vetschera P,Glasl S,Chmyrov A,Richter K,Ntziachristos V,Stiel AC

    更新日期：2019-09-20 00:00:00

  • Fragment Assembly Approach Based on Graph/Network Theory with Quantum Chemistry Verifications for Assigning Multidimensional NMR Signals in Metabolite Mixtures.

    abstract：:The abundant observation of chemical fragment information for molecular complexities is a major advantage of biological NMR analysis. Thus, the development of a novel technique for NMR signal assignment and metabolite identification may offer new possibilities for exploring molecular complexities. We propose a new sig...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00894

    authors： Ito K,Tsutsumi Y,Date Y,Kikuchi J

    更新日期：2016-04-15 00:00:00

  • Yersinia inhibits host signaling by acetylating MAPK kinases.

    abstract：:Pathogenic Yersinia spp. secrete the effector YopJ (YopP) into host cells to counteract cytokine production and to induce programmed cell death (apoptosis). YopJ achieves these aims by inactivating mitogen-activated protein kinase (MAPK) and nuclear factor kappaB signaling pathways. YopJ was shown to bind to members o...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb600261k

    authors： Bliska JB

    更新日期：2006-07-21 00:00:00

  • A Fluorescent Hsp90 Probe Demonstrates the Unique Association between Extracellular Hsp90 and Malignancy in Vivo.

    abstract：:Extracellular expression of heat shock protein 90 (eHsp90) by tumor cells is correlated with malignancy. Development of small molecule probes that can detect eHsp90 in vivo may therefore have utility in the early detection of malignancy. We synthesized a cell impermeable far-red fluorophore-tagged Hsp90 inhibitor to t...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00006

    authors： Crowe LB,Hughes PF,Alcorta DA,Osada T,Smith AP,Totzke J,Loiselle DR,Lutz ID,Gargesha M,Roy D,Roques J,Darr D,Lyerly HK,Spector NL,Haystead TAJ

    更新日期：2017-04-21 00:00:00

  • Small molecules that recapitulate the early steps of urodele amphibian limb regeneration and confer multipotency.

    abstract：:In urodele amphibians, an early step in limb regeneration is skeletal muscle fiber dedifferentiation into a cellulate that proliferates to contribute new limb tissue. However, mammalian muscle cannot dedifferentiate after injury. We have developed a novel, small-molecule-based method to induce dedifferentiation in mam...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200532v

    authors： Kim WH,Jung DW,Kim J,Im SH,Hwang SY,Williams DR

    更新日期：2012-04-20 00:00:00

  • Chemical modification of conotoxins to improve stability and activity.

    abstract：:Conotoxins are small disulfide-rich peptides from the venom of cone snails. Along with other conopeptides, they target a wide range of membrane receptors, ion channels, and transporters, and because of their high potency and selectivity for defined subtypes of these receptors, they have attracted a great deal of atten...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb700091j

    authors： Craik DJ,Adams DJ

    更新日期：2007-07-20 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

  • Exploration of type II binding mode: A privileged approach for kinase inhibitor focused drug discovery?

    abstract：:The ATP site of kinases displays remarkable conformational flexibility when accommodating chemically diverse small molecule inhibitors. The so-called activation segment, whose conformation controls catalytic activity and access to the substrate binding pocket, can undergo a large conformational change with the active ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb500129t

    authors： Zhao Z,Wu H,Wang L,Liu Y,Knapp S,Liu Q,Gray NS

    更新日期：2014-06-20 00:00:00

  • YTHDF2 Recognition of N1-Methyladenosine (m1A)-Modified RNA Is Associated with Transcript Destabilization.

    abstract：:Epitranscriptomic modifications play an important role in RNA function and can impact gene expression. Here, we apply a chemical proteomics approach to investigate readers of N1-methyladenosine (m1A), a poorly characterized modification on mammalian mRNA. We find that YTHDF proteins, known m6A readers, recognize m1A-m...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00655

    authors： Seo KW,Kleiner RE

    更新日期：2020-01-17 00:00:00

  • Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma.

    abstract：:Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive pro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00615

    authors： Childs-Disney JL,Disney MD

    更新日期：2016-02-19 00:00:00

  • Transferrin Cycle and Clinical Roles of Citrate and Ascorbate in Improved Iron Metabolism.

    abstract：:Fe(III) delivery from blood plasma to cells via the transferrin (Tf) cycle was studied intensively due to its crucial role in Fe homeostasis. Tf-cycle disruptions are linked to anemia, infections, immunodeficiency, and neurodegeneration. Biolayer interferometry (BLI) enabled direct kinetic and thermodynamic measuremen...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b01100

    authors： Levina A,Lay PA

    更新日期：2019-05-17 00:00:00