当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol.

Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol.

Abstract：

:The diterpene cyclase CotB2 catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to the tricyclic cyclooctat-9-en-7-ol, which is characterized by a 5-8-5-fused ring skeleton. We have previously proposed a cyclization cascade involving a unique carbon-carbon bond rearrangement combined with multiple hydride shifts, all occurring at a single active site. Here, we report the first high-resolution X-ray crystal structure of CotB2 with bound substrate analog geranylgeranyl thiodiphosphate (GGSPP). In the GGSPP-bound form, GGSPP folds into a unique S-shaped conformation that probably reflects the substrate-bound state prior to ionization of the substrate GGPP. The folded framework of GGSPP is surrounded by hydrophobic residues and several aromatic and asparagine residues that are well-positioned to stabilize a series of reactive carbocation intermediates through a combination of cation-π and dipole charge interactions. The combined crystal structures and mutagenesis-based biochemical assays provide a structural basis for exquisite control of ring formation and stereochemistry during CotB2 catalysis.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Tomita T,Kim SY,Teramoto K,Meguro A,Ozaki T,Yoshida A,Motoyoshi Y,Mori N,Ishigami K,Watanabe H,Nishiyama M,Kuzuyama T

doi

10.1021/acschembio.7b00154

subject

Has Abstract

pub_date

2017-06-16 00:00:00

pages

1621-1628

issue

6

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • 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

  • A chemical genetic approach for covalent inhibition of analogue-sensitive aurora kinase.

    abstract：:The perturbation of protein kinases with small organic molecules is a powerful approach to dissect kinase function in complex biological systems. Covalent kinase inhibitors that target thiols in the ATP binding pocket of the kinase domain proved to be ideal reagents for the investigation of highly dynamic cellular pro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200465c

    authors： Koch A,Rode HB,Richters A,Rauh D,Hauf S

    更新日期：2012-04-20 00:00:00

  • Surprising Non-Additivity of Methyl Groups in Drug-Kinase Interaction.

    abstract：:Drug optimization is guided by biophysical methods with increasing popularity. In the context of lead structure modifications, the introduction of methyl groups is a simple but potentially powerful approach. Hence, it is crucial to systematically investigate the influence of ligand methylation on biophysical character...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00476

    authors： Wienen-Schmidt B,Schmidt D,Gerber HD,Heine A,Gohlke H,Klebe G

    更新日期：2019-12-20 00:00:00

  • Mass spectrometry-based detection and assignment of protein posttranslational modifications.

    abstract：:Recent advances in mass spectrometry (MS)-based proteomics allow the identification and quantitation of thousands of posttranslational modification (PTM) sites in a single experiment. This follows from the development of more effective class enrichment strategies, new high performance instrumentation and bioinformatic...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb500904b

    authors： Doll S,Burlingame AL

    更新日期：2015-01-16 00:00:00

  • Engineering the polyproline II propensity of a class II major histocompatibility complex ligand peptide.

    abstract：:Our immune system constantly samples peptides found inside the body as a means to detect foreign pathogens, infected cells, and tumorous cells. T cells, which carry out the critical task of distinguishing self from nonself peptides, can only survey peptides that are presented by the major histocompatibility complex pr...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400594q

    authors： Unudurthi SD,Hotta K,Kim CY

    更新日期：2013-11-15 00:00:00

  • Analysis of amyloid nanostructures using photo-cross-linking: in situ comparison of three widely used photo-cross-linkers.

    abstract：:Photoinduced cross-linking (PIC) has become a powerful tool in chemical biology for the identification and mapping of stable or transient interactions between biomacromolecules and their (unknown) ligands. However, the value of PIC for in vitro and in vivo structural proteomics can be realized only if cross-linking re...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400731s

    authors： Preston GW,Radford SE,Ashcroft AE,Wilson AJ

    更新日期：2014-03-21 00:00:00

  • New Simocyclinones: Surprising Evolutionary and Biosynthetic Insights.

    abstract：:Simocyclinone D8 (1, SD8) has attracted attention due to its highly complex hybrid structure and the unusual way it inhibits bacterial DNA gyrase by preventing DNA binding to the enzyme. Although a hypothesis explaining simocyclinone biosynthesis has been previously proposed, little was proven in vivo due to the genet...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00669

    authors： Bilyk O,Brötz E,Tokovenko B,Bechthold A,Paululat T,Luzhetskyy A

    更新日期：2016-01-15 00:00:00

  • Furoxan Nitric Oxide Donors Disperse Pseudomonas aeruginosa Biofilms, Accelerate Growth, and Repress Pyoverdine Production.

    abstract：:The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their effi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00256

    authors： Poh WH,Barraud N,Guglielmo S,Lazzarato L,Rolando B,Fruttero R,Rice SA

    更新日期：2017-08-18 00:00:00

  • Use of calculated cation-pi binding energies to predict relative strengths of nicotinic acetylcholine receptor agonists.

    abstract：:Agonists and antagonists of the nicotinic acetylcholine receptor (nAChR) are used to treat nicotine addiction, neuromuscular disorders, and neurological diseases. In designing small molecule therapeutics with the nAChR as a target, it is useful to identify chemical parameters that correlate with ability to activate th...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb800189y

    authors： Tantama M,Licht S

    更新日期：2008-11-21 00:00:00

  • Novel inhibitors of human DOPA decarboxylase extracted from Euonymus glabra Roxb.

    abstract：:Dopamine, a biogenic amine with important biological functions, is produced from l-DOPA by DOPA decarboxylase (DDC). DDC is a potential target to modulate the production of dopamine in several pathological states. Known inhibitors of DDC have been used for treatment of Parkinson's disease but suffered low specificity ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500009r

    authors： Ren J,Zhang Y,Jin H,Yu J,Zhou Y,Wu F,Zhang W

    更新日期：2014-04-18 00:00:00

  • Impaired transport of nucleotides in a mitochondrial carrier explains severe human genetic diseases.

    abstract：:The mitochondrial ADP/ATP carrier (AAC) is a prominent actor in the energetic regulation of the cell, importing ADP into the mitochondria and exporting ATP toward the cytoplasm. Severe genetic diseases have been ascribed to specific mutations in this membrane protein. How minute, well-localized modifications of the tr...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300012j

    authors： Ravaud S,Bidon-Chanal A,Blesneac I,Machillot P,Juillan-Binard C,Dehez F,Chipot C,Pebay-Peyroula E

    更新日期：2012-07-20 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

  • Targeting native adult heart progenitors with cardiogenic small molecules.

    abstract：:Targeting native progenitors with small molecule pharmaceuticals that direct cell fate decisions is an attractive approach for regenerative medicine. Here, we show that 3,5-disubstituted isoxazoles (Isx), stem cell-modulator small molecules originally recovered in a P19 embryonal carcinoma cell-based screen, directed ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200525q

    authors： Russell JL,Goetsch SC,Aguilar HR,Frantz DE,Schneider JW

    更新日期：2012-06-15 00:00:00

  • Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.

    abstract：:The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis, and treatment resistance, yet therapeutic targeting, drug discovery, or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical pro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00709

    authors： Heinzlmeir S,Kudlinzki D,Sreeramulu S,Klaeger S,Gande SL,Linhard V,Wilhelm M,Qiao H,Helm D,Ruprecht B,Saxena K,Médard G,Schwalbe H,Kuster B

    更新日期：2016-12-16 00:00:00

  • Diverse Class 2 CRISPR-Cas Effector Proteins for Genome Engineering Applications.

    abstract：:CRISPR-Cas genome editing technologies have revolutionized modern molecular biology by making targeted DNA edits simple and scalable. These technologies are developed by domesticating naturally occurring microbial adaptive immune systems that display wide diversity of functionality for targeted nucleic acid cleavage. ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/acschembio.7b00800

    authors： Pyzocha NK,Chen S

    更新日期：2018-02-16 00:00:00

  • Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.

    abstract：:Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermo...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00895

    authors： Glöckner S,Ngo K,Sager CP,Hüfner-Wulsdorf T,Heine A,Klebe G

    更新日期：2020-03-20 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

  • Retroviral display in gene therapy, protein engineering, and vaccine development.

    abstract：:The display and analysis of proteins expressed on biological surfaces has become an attractive tool for the study of molecular interactions in enzymology, protein engineering, and high-throughput screening. Among the growing number of established display systems, retroviruses offer a unique and fully mammalian platfor...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb100285n

    authors： Urban JH,Merten CA

    更新日期：2011-01-21 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

  • Structural and Biosynthetic Analysis of the Fabrubactins, Unusual Siderophores from Agrobacterium fabrum Strain C58.

    abstract：:Siderophores are iron-chelating molecules produced by microorganisms and plants to acquire exogenous iron. Siderophore biosynthetic enzymology often produces elaborate and unique molecules through unusual reactions to enable specific recognition by the producing organisms. Herein, we report the structure of two sidero...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00809

    authors： Vinnik V,Zhang F,Park H,Cook TB,Throckmorton K,Pfleger BF,Bugni TS,Thomas MG

    更新日期：2021-01-15 00:00:00

  • Xanthohumol impairs autophagosome maturation through direct inhibition of valosin-containing protein.

    abstract：:Autophagy is a bulk, nonspecific protein degradation pathway that is involved in the pathogenesis of cancer and neurodegenerative disease. Here, we observed that xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupulus L.) and beer, modulates autophagy. By using XN-immobilized beads, valosin-containing...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200492h

    authors： Sasazawa Y,Kanagaki S,Tashiro E,Nogawa T,Muroi M,Kondoh Y,Osada H,Imoto M

    更新日期：2012-05-18 00:00:00

  • Heterologous Biosynthesis of Type II Polyketide Products Using E. coli.

    abstract：:The heterologous biosynthesis of complex natural products has enabled access to polyketide, nonribosomal peptide, isoprenoid, and other compounds with wide-spanning societal value. Though several surrogate host systems exist, Escherichia coli is often a preferred choice due to its rapid growth kinetics and extensive m...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00827

    authors： Liu X,Hua K,Liu D,Wu ZL,Wang Y,Zhang H,Deng Z,Pfeifer BA,Jiang M

    更新日期：2020-05-15 00:00:00

  • Quantitative analysis of T cell receptor complex interaction sites using genetically encoded photo-cross-linkers.

    abstract：:The T cell receptor (TCR)-cluster of differentiation 3 (CD3) signaling complex plays an important role in initiation of adaptive immune responses, but weak interactions have obstructed delineation of the individual TCR-CD3 subunit interactions during T cell signaling. Here, we demonstrate that unnatural amino acids (U...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500351s

    authors： Wang W,Li T,Felsovalyi K,Chen C,Cardozo T,Krogsgaard M

    更新日期：2014-09-19 00:00:00

  • Characterization of CYP115 As a Gibberellin 3-Oxidase Indicates That Certain Rhizobia Can Produce Bioactive Gibberellin A4.

    abstract：:The gibberellin (GA) phytohormones are produced not only by plants but also by fungi and bacteria. Previous characterization of a cytochrome P450 (CYP)-rich GA biosynthetic operon found in many symbiotic, nitrogen-fixing rhizobia led to the elucidation of bacterial GA biosynthesis and implicated GA9 as the final produ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b01038

    authors： Nett RS,Contreras T,Peters RJ

    更新日期：2017-04-21 00:00:00

  • Histo-Blood Group Antigen Presentation Is Critical for Binding of Norovirus VLP to Glycosphingolipids in Model Membranes.

    abstract：:Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane-associated glycans is more restricted than that of g...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00152

    authors： Nasir W,Frank M,Kunze A,Bally M,Parra F,Nyholm PG,Höök F,Larson G

    更新日期：2017-05-19 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

  • Progressive Stereo Locking (PSL): A Residual Dipolar Coupling Based Force Field Method for Determining the Relative Configuration of Natural Products and Other Small Molecules.

    abstract：:Establishing the relative configuration of a bioactive natural product represents the most challenging part in determining its structure. Residual dipolar couplings (RDCs) are sensitive probes of the relative spatial orientation of internuclear vectors. We adapted a force field structure calculation methodology to all...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00281

    authors： Cornilescu G,Ramos Alvarenga RF,Wyche TP,Bugni TS,Gil RR,Cornilescu CC,Westler WM,Markley JL,Schwieters CD

    更新日期：2017-08-18 00:00:00

  • Efficient NQO1 substrates are potent and selective anticancer agents.

    abstract：:A major goal of personalized medicine in oncology is the identification of drugs with predictable efficacy based on a specific trait of the cancer cell, as has been demonstrated with gleevec (presence of Bcr-Abl protein), herceptin (Her2 overexpression), and iressa (presence of a specific EGFR mutation). This is a cha...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb4005832

    authors： Parkinson EI,Bair JS,Cismesia M,Hergenrother PJ

    更新日期：2013-10-18 00:00:00

  • Peptide-based investigation of the Escherichia coli RNA polymerase σ(70):core interface as target site.

    abstract：:The number of bacterial strains that are resistant against antibiotics increased dramatically during the past decades. This fact stresses the urgent need for the development of new antibacterial agents with novel modes of action targeting essential enzymes such as RNA polymerase (RNAP). Bacterial RNAP is a large multi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb3005758

    authors： Hüsecken K,Negri M,Fruth M,Boettcher S,Hartmann RW,Haupenthal J

    更新日期：2013-04-19 00:00:00

  • Insights into substrate and metal binding from the crystal structure of cyanobacterial aldehyde deformylating oxygenase with substrate bound.

    abstract：:The nonheme diiron enzyme cyanobacterial aldehyde deformylating oxygenase, cADO, catalyzes the highly unusual deformylation of aliphatic aldehydes to alkanes and formate. We have determined crystal structures for the enzyme with a long-chain water-soluble aldehyde and medium-chain carboxylic acid bound to the active s...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500343j

    authors： Buer BC,Paul B,Das D,Stuckey JA,Marsh EN

    更新日期：2014-11-21 00:00:00