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 biosynthesi...

journal_title：ACS chemical biology

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

更新日期：2015-11-20 00:00:00

abstract：:Lasso peptides are bacterial ribosomally synthesized and post-translationally modified peptides. They have sparked increasing interest in peptide-based drug development because of their compact, interlocked structure, which offers superior stability and protein-binding capacity. Disulfide bond-containing lasso peptide...

journal_title：ACS chemical biology

authors： Li Y,Ducasse R,Zirah S,Blond A,Goulard C,Lescop E,Giraud C,Hartke A,Guittet E,Pernodet JL,Rebuffat S

更新日期：2015-11-20 00:00:00

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

authors： Zhang Y,O'Brien PJ

更新日期：2015-11-20 00:00:00

abstract：:Phenotypic screening of compound libraries is a significant trend in drug discovery, yet success can be hindered by difficulties in identifying the underlying cellular targets. Current approaches rely on tethering bioactive compounds to a capture tag or surface to allow selective enrichment of interacting proteins for...

journal_title：ACS chemical biology

authors： Ohana RF,Kirkland TA,Woodroofe CC,Levin S,Uyeda HT,Otto P,Hurst R,Robers MB,Zimmerman K,Encell LP,Wood KV

更新日期：2015-10-16 00:00:00

abstract：:Hypoxia induces a complex circuit of gene expression that drives tumor progression and increases drug resistance. Defining these changes allows for an understanding of how hypoxia alters tumor biology and informs design of lead therapeutics. We probed the role of microRNA-544 (miR-544), which silences mammalian target...

journal_title：ACS chemical biology

authors： Haga CL,Velagapudi SP,Strivelli JR,Yang WY,Disney MD,Phinney DG

更新日期：2015-10-16 00:00:00

abstract：:Sugar aminotransferases (SATs) are an important class of tailoring enzymes that catalyze the 5'-pyridoxal phosphate (PLP)-dependent stereo- and regiospecific installation of an amino group from an amino acid donor (typically L-Glu or L-Gln) to a corresponding ketosugar nucleotide acceptor. Herein we report the strateg...

journal_title：ACS chemical biology

authors： Wang F,Singh S,Xu W,Helmich KE,Miller MD,Cao H,Bingman CA,Thorson JS,Phillips GN Jr

更新日期：2015-09-18 00:00:00

abstract：:The flavo-enzyme DprE1 catalyzes a key epimerization step in the decaprenyl-phosphoryl d-arabinose (DPA) pathway, which is essential for mycobacterial cell wall biogenesis and targeted by several new tuberculosis drug candidates. Here, using differential radiolabeling with DPA precursors and high-resolution fluorescen...

journal_title：ACS chemical biology

authors： Brecik M,Centárová I,Mukherjee R,Kolly GS,Huszár S,Bobovská A,Kilacsková E,Mokošová V,Svetlíková Z,Šarkan M,Neres J,Korduláková J,Cole ST,Mikušová K

更新日期：2015-07-17 00:00:00

abstract：:Membrane proteins perform their functions within or on the lipid membrane, and lipid compositions are known to affect membrane protein integration and activity. Recently, the geometric aspect of membrane curvature was shown to play an important role in membrane protein behavior. Certain membrane proteins are known to ...

journal_title：ACS chemical biology

authors： Fujii S,Matsuura T,Yomo T

更新日期：2015-07-17 00:00:00

abstract：:The genetic integrity of each organism depends on the faithful segregation of its genome during mitosis. To meet this challenge, a cellular surveillance mechanism, termed the spindle assembly checkpoint (SAC), evolved that monitors the correct attachment of chromosomes and blocks progression through mitosis if correct...

journal_title：ACS chemical biology

authors： Kastl J,Braun J,Prestel A,Möller HM,Huhn T,Mayer TU

更新日期：2015-07-17 00:00:00

abstract：:Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-κB signaling in human cells. NSC697923 and BAY 11-7082 both i...

journal_title：ACS chemical biology

authors： Hodge CD,Edwards RA,Markin CJ,McDonald D,Pulvino M,Huen MS,Zhao J,Spyracopoulos L,Hendzel MJ,Glover JN

更新日期：2015-07-17 00:00:00

abstract：:We report progress toward a general strategy for mimicking the recognition properties of specific α-helices within natural proteins through the use of oligomers that are less susceptible than conventional peptides to proteolysis. The oligomers contain both α- and β-amino acid residues, with the density of the β subuni...

journal_title：ACS chemical biology

authors： Peterson-Kaufman KJ,Haase HS,Boersma MD,Lee EF,Fairlie WD,Gellman SH

更新日期：2015-07-17 00:00:00

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

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

abstract：:Streptolysin S (SLS) is a post-translationally modified peptide cytolysin that is produced by the human pathogen Streptococcus pyogenes. SLS belongs to a large family of azole-containing natural products that are biosynthesized via an evolutionarily conserved pathway. SLS is an important virulence factor during S. pyo...

journal_title：ACS chemical biology

authors： Maxson T,Deane CD,Molloy EM,Cox CL,Markley AL,Lee SW,Mitchell DA

更新日期：2015-05-15 00:00:00

abstract：:Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii, the causative agents of severe malaria and toxoplasmosis, respectively, undergo several critical developmental transitions during their lifecycle. Most important for human pathogenesis is the asexual cycle, in which parasites undergo rounds...

journal_title：ACS chemical biology

authors： Howard BL,Harvey KL,Stewart RJ,Azevedo MF,Crabb BS,Jennings IG,Sanders PR,Manallack DT,Thompson PE,Tonkin CJ,Gilson PR

更新日期：2015-04-17 00:00:00

abstract：:Various potential G-quadruplex forming sequences present in the genome offer a platform to modulate their function by means of stabilizing molecules. Though G-quadruplex structures exhibit diverse structural topologies, the presence of G-quartets as a common structural element makes the design of topology specific lig...

journal_title：ACS chemical biology

authors： Dhamodharan V,Harikrishna S,Bhasikuttan AC,Pradeepkumar PI

更新日期：2015-03-20 00:00:00

abstract：:Bromodomains are protein modules that bind to acetylated lysine residues. Their interaction with histone proteins suggests that they function as "readers" of histone lysine acetylation, a component of the proposed "histone code". Bromodomain-containing proteins are often found as components of larger protein complexes...

journal_title：ACS chemical biology

authors： Brand M,Measures AR,Wilson BG,Cortopassi WA,Alexander R,Höss M,Hewings DS,Rooney TP,Paton RS,Conway SJ

更新日期：2015-01-16 00:00:00

abstract：:The quest for ever more selective kinase inhibitors as potential future drugs has yielded a large repertoire of chemical probes that are selective for specific kinase conformations. These probes have been useful tools to obtain structural snapshots of kinase conformational plasticity. Similarly, kinetic and thermodyna...

journal_title：ACS chemical biology

authors： Tong M,Seeliger MA

更新日期：2015-01-16 00:00:00

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

authors： Doll S,Burlingame AL

更新日期：2015-01-16 00:00:00

abstract：:Epigenetic regulation is directed, in part, by the correlated placement of histone post-translational modifications, but the mechanisms controlling correlated modifications are incompletely understood. Correlations arise from crosstalk among modifications and are frequently attributed to protein-protein interactions t...

journal_title：ACS chemical biology

authors： Kornacki JR,Stuparu AD,Mrksich M

更新日期：2015-01-16 00:00:00

abstract：:Formylglycine (fGly) is a catalytically essential residue found almost exclusively in the active sites of type I sulfatases. Formed by post-translational oxidation of cysteine or serine side chains, this aldehyde-functionalized residue participates in a unique and highly efficient catalytic mechanism for sulfate ester...

journal_title：ACS chemical biology

authors： Appel MJ,Bertozzi CR

更新日期：2015-01-16 00:00:00

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

authors： Pott M,Schmidt MJ,Summerer D

更新日期：2014-12-19 00:00:00

abstract：:The indole side chain of tryptophan has latent nucleophilic reactivity at both N1 and all six (nonbridgehead) carbons, which is not generally manifested in post-translational reactions of proteins. On the other hand, all seven positions can be prenylated by the primary metabolite Δ(2)-isopentenyl diphosphate by dimeth...

journal_title：ACS chemical biology

authors： Walsh CT

更新日期：2014-12-19 00:00:00

abstract：:The Pygo-BCL9 complex is a chromatin reader, facilitating β-catenin-mediated oncogenesis, and is thus emerging as a potential therapeutic target for cancer. Its function relies on two ligand-binding surfaces of Pygo's PHD finger that anchor the histone H3 tail methylated at lysine 4 (H3K4me) with assistance from the B...

journal_title：ACS chemical biology

authors： Miller TC,Rutherford TJ,Birchall K,Chugh J,Fiedler M,Bienz M

更新日期：2014-12-19 00:00:00

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

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

abstract：:Epigenetic regulation of gene expression is essential in many biological processes, and its deregulation contributes to pathology including tumor formation. We used an image-based cell assay that measures the induction of a silenced GFP-estrogen receptor reporter to identify novel classes of small molecules involved i...

journal_title：ACS chemical biology

authors： Tran TA,Wichterman-Kouznetsova J,Varghese D,Huang R,Huang W,Becker M,Austin CP,Inglese J,Johnson RL,Martinez ED

更新日期：2014-11-21 00:00:00

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

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

更新日期：2014-11-21 00:00:00

abstract：:Caged compounds are useful tools for precise spatiotemporal modulation of cell functions, but in most cases uncaging requires ultraviolet (UV) light, which is cytotoxic and has limited tissue penetration. Therefore, caged compounds that can be activated by longer-wavelength light are required. Here we describe a novel...

journal_title：ACS chemical biology

authors： Umeda N,Takahashi H,Kamiya M,Ueno T,Komatsu T,Terai T,Hanaoka K,Nagano T,Urano Y

更新日期：2014-10-17 00:00:00

abstract：:Despite being extensively characterized structurally and biochemically, the functional role of histone deacetylase 8 (HDAC8) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics method...

journal_title：ACS chemical biology

authors： Olson DE,Udeshi ND,Wolfson NA,Pitcairn CA,Sullivan ED,Jaffe JD,Svinkina T,Natoli T,Lu X,Paulk J,McCarren P,Wagner FF,Barker D,Howe E,Lazzaro F,Gale JP,Zhang YL,Subramanian A,Fierke CA,Carr SA,Holson EB

更新日期：2014-10-17 00:00:00

abstract：:Calicheamicin γ1I (1) is an enediyne antitumor compound produced by Micromonospora echinospora spp. calichensis, and its biosynthetic gene cluster has been previously reported. Despite extensive analysis and biochemical study, several genes in the biosynthetic gene cluster of 1 remain functionally unassigned. Using a ...

journal_title：ACS chemical biology

authors： Elshahawi SI,Ramelot TA,Seetharaman J,Chen J,Singh S,Yang Y,Pederson K,Kharel MK,Xiao R,Lew S,Yennamalli RM,Miller MD,Wang F,Tong L,Montelione GT,Kennedy MA,Bingman CA,Zhu H,Phillips GN Jr,Thorson JS

更新日期：2014-10-17 00:00:00

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

authors： Daeffler KN,Lester HA,Dougherty DA

更新日期：2014-10-17 00:00:00

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

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

abstract：:Antimicrobial peptides (AMPs) kill bacteria mainly through the perturbation of their membranes and are promising compounds to fight drug resistance. Models of the mechanism of AMPs-induced membrane perturbation were developed based on experiments in liposomes, but their relevance for bacterial killing is debated. We d...

journal_title：ACS chemical biology

authors： Roversi D,Luca V,Aureli S,Park Y,Mangoni ML,Stella L

更新日期：2014-09-19 00:00:00

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

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

更新日期：2014-09-19 00:00:00

abstract：:This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli bu...

journal_title：ACS chemical biology

authors： Wang G,Hanke ML,Mishra B,Lushnikova T,Heim CE,Chittezham Thomas V,Bayles KW,Kielian T

更新日期：2014-09-19 00:00:00

abstract：:Polyhalogenated dibenzo-p-dioxins are arguably among the most toxic molecules known to man. In addition to anthropogenic sources, marine invertebrates also harbor polybrominated dibenzo-p-dioxins of as yet unknown biogenic origin. Here, we report that the bmp gene locus in marine bacteria, a recently characterized sou...

journal_title：ACS chemical biology

authors： Agarwal V,Moore BS

更新日期：2014-09-19 00:00:00

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

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

abstract：:Cocaine esterase (CocE) is known as the most efficient natural enzyme for cocaine hydrolysis. The major obstacle to the clinical application of wild-type CocE is the thermoinstability with a half-life of only ∼12 min at 37 °C. The previously designed T172R/G173Q mutant (denoted as enzyme E172-173) with an improved in ...

journal_title：ACS chemical biology

authors： Fang L,Chow KM,Hou S,Xue L,Chen X,Rodgers DW,Zheng F,Zhan CG

更新日期：2014-08-15 00:00:00

abstract：:Kinases constitute an important class of therapeutic targets being explored both by academia and the pharmaceutical industry. The major focus of this effort was directed toward the identification of ATP competitive inhibitors. Although it has long been recognized that the intracellular concentration of ATP is very dif...

journal_title：ACS chemical biology

authors： Thorarensen A,Banker ME,Fensome A,Telliez JB,Juba B,Vincent F,Czerwinski RM,Casimiro-Garcia A

更新日期：2014-07-18 00:00:00

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

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

abstract：:The heat shock response is an evolutionarily conserved, stress-responsive signaling pathway that adapts cellular proteostasis in response to pathologic insult. In metazoans, the heat shock response primarily functions through the posttranslational activation of heat shock factor 1 (HSF1), a stress-responsive transcrip...

journal_title：ACS chemical biology

authors： Ryno LM,Genereux JC,Naito T,Morimoto RI,Powers ET,Shoulders MD,Wiseman RL

更新日期：2014-06-20 00:00:00