Exploiting structural analysis, in silico screening, and serendipity to identify novel inhibitors of drug-resistant falciparum malaria.

abstract：:To discover chemical probes to further under-stand the function of individual DNA polymerases, we established a generally applicable high-throughput screening. By applying this technique we discovered three novel inhibitor classes of human DNA polymerase λ (DNA Pol λ), a key enzyme to maintain the genetic integrity of...

journal_title：ACS chemical biology

authors： Strittmatter T,Bareth B,Immel TA,Huhn T,Mayer TU,Marx A

更新日期：2011-04-15 00:00:00

abstract：:RNA modifications play important roles in RNA structures and regulation of gene expression and translation. We report the first RNA modification on the phosphate, the RNA phosphorothioate (PS) modification, discovered in both prokaryotes and eukaryotes. The PS modification is also first reported on nucleic acids of eu...

journal_title：ACS chemical biology

authors： Wu Y,Tang Y,Dong X,Zheng YY,Haruehanroengra P,Mao S,Lin Q,Sheng J

更新日期：2020-06-19 00:00:00

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

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

更新日期：2012-04-20 00:00:00

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

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

更新日期：2019-12-20 00:00:00

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

authors： Hull CM,Anmangandla A,Bevilacqua PC

更新日期：2016-04-15 00:00:00

abstract：:Light-activated protein domains provide a convenient, modular, and genetically encodable sensor for optogenetics and optobiology. Although these domains have now been deployed in numerous systems, the precise mechanism of photoactivation and the accompanying structural dynamics that modulate output domain activity rem...

journal_title：ACS chemical biology

authors： Iuliano JN,Collado JT,Gil AA,Ravindran PT,Lukacs A,Shin S,Woroniecka HA,Adamczyk K,Aramini JM,Edupuganti UR,Hall CR,Greetham GM,Sazanovich IV,Clark IP,Daryaee T,Toettcher JE,French JB,Gardner KH,Simmerling CL,Meech

更新日期：2020-10-16 00:00:00

abstract：:Platinum-based drugs have been used to successfully treat diverse cancers for several decades. Cisplatin, the original compound of this class, cross-links DNA, resulting in cell cycle arrest and cell death via apoptosis. Cisplatin is effective against several tumor types, yet it exhibits toxic side effects and tumors ...

journal_title：ACS chemical biology

authors： Cheung-Ong K,Song KT,Ma Z,Shabtai D,Lee AY,Gallo D,Heisler LE,Brown GW,Bierbach U,Giaever G,Nislow C

更新日期：2012-11-16 00:00:00

abstract：:A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small...

journal_title：ACS chemical biology

authors： Gaffney A,Nangarlia A,Ang CG,Gossert S,Rashad Ahmed AA,Hossain MA,Abrams CF,Smith AB 3rd,Chaiken I

更新日期：2021-01-15 00:00:00

abstract：:Aminoglycoside antibiotics were among the first antibiotics discovered and used clinically. Although they have never completely fallen out of favor, their importance has waned due to the emergence of other broad-spectrum antibiotics with fewer side effects. Today, with the dramatically increasing rate of infections ca...

journal_title：ACS chemical biology

authors： Becker B,Cooper MA

更新日期：2013-01-18 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：: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

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

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：:Dysregulated activity of the protease matriptase is a key contributor to aggressive tumor growth, cancer metastasis, and osteoarthritis. Methods for the detection and quantification of matriptase activity and inhibition would be useful tools. To address this need, we developed a matriptase-sensitive protein biosensor ...

journal_title：ACS chemical biology

authors： Mitchell AC,Alford SC,Hunter SA,Kannan D,Parra Sperberg RA,Chang CH,Cochran JR

更新日期：2018-01-19 00:00:00

abstract：:Matrix metalloproteases (MMPs) are a large family of zinc-dependent endopeptidases involved in a diverse set of physiological and pathological processes, most notably in cancer. Current methods for imaging and quantifying MMP activity lack sufficient selectivity and spatiotemporal resolution to allow studies of specif...

journal_title：ACS chemical biology

authors： Amara N,Tholen M,Bogyo M

更新日期：2018-09-21 00:00:00

abstract：:Determining the impact of lipid electrophile-mediated protein damage that occurs during oxidative stress requires a comprehensive analysis of electrophile targets adducted under pathophysiological conditions. Incorporation of ω-alkynyl linoleic acid into the phospholipids of macrophages prior to activation by Kdo2-lip...

journal_title：ACS chemical biology

authors： Beavers WN,Rose KL,Galligan JJ,Mitchener MM,Rouzer CA,Tallman KA,Lamberson CR,Wang X,Hill S,Ivanova PT,Brown HA,Zhang B,Porter NA,Marnett LJ

更新日期：2017-08-18 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：:Stapled peptides have great potential as modulators of protein-protein interactions (PPIs). However, there is a vast landscape of chemical features that can be varied for any given peptide, and identifying a set of features that maximizes cellular uptake and subsequent target engagement remains a key challenge. Herein...

journal_title：ACS chemical biology

authors： Wu Y,Kaur A,Fowler E,Wiedmann MM,Young R,Galloway WRJD,Olsen L,Sore HF,Chattopadhyay A,Kwan TT,Xu W,Walsh SJ,de Andrade P,Janecek M,Arumugam S,Itzhaki LS,Lau YH,Spring DR

更新日期：2019-03-15 00:00:00

abstract：:Nonribosomal peptides are important natural products biosynthesized by nonribosomal peptide synthetases (NRPSs). Adenylation (A) domains of NRPSs are highly specific for the substrate they recognize. This recognition is determined by 10 residues in the substrate-binding pocket, termed the specificity code. This findin...

journal_title：ACS chemical biology

authors： Throckmorton K,Vinnik V,Chowdhury R,Cook T,Chevrette MG,Maranas C,Pfleger B,Thomas MG

更新日期：2019-09-20 00:00:00

abstract：:Peptide-recognizing G protein-coupled receptors (GPCRs) are promising therapeutic targets but often resist drug discovery efforts. Determination of crystal structures for peptide-binding GPCRs has provided opportunities to explore structure-based methods in lead development. Molecular docking screens of two chemical l...

journal_title：ACS chemical biology

authors： Ranganathan A,Heine P,Rudling A,Plückthun A,Kummer L,Carlsson J

更新日期：2017-03-17 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：: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

authors： Deochand DK,Meariman JK,Grove A

更新日期：2016-07-15 00:00:00

abstract：:Nature uses four methods of carbon chain elongation for the production of 2-ketoacids, fatty acids, polyketides, and isoprenoids. Using a combination of quantum mechanical (QM) modeling, protein-substrate modeling, and protein and metabolic engineering, we have engineered the enzymes involved in leucine biosynthesis f...

journal_title：ACS chemical biology

authors： Marcheschi RJ,Li H,Zhang K,Noey EL,Kim S,Chaubey A,Houk KN,Liao JC

更新日期：2012-04-20 00:00:00

abstract：:O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function. Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells. Here, we develop...

journal_title：ACS chemical biology

authors： Li J,Li Z,Duan X,Qin K,Dang L,Sun S,Cai L,Hsieh-Wilson LC,Wu L,Yi W

更新日期：2019-01-18 00:00:00

abstract：:The human ClpP proteolytic complex (HsClpP) is a serine protease located in the mitochondrial matrix and participates in the maintenance of the mitochondrial proteome among other cellular functions. HsClpP typically forms a multimeric complex with the AAA+ protein unfoldase HsClpX. Notably, compared to that of normal,...

journal_title：ACS chemical biology

authors： Wong KS,Houry WA

更新日期：2019-11-15 00:00:00

abstract：:BRD4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding sites and competitively inhibit BET protein interaction with acetylated chromatin...

journal_title：ACS chemical biology

authors： Olp MD,Sprague DJ,Goetz CJ,Kathman SG,Wynia-Smith SL,Shishodia S,Summers SB,Xu Z,Statsyuk AV,Smith BC

更新日期：2020-04-17 00:00:00

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

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

abstract：:The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used t...

journal_title：ACS chemical biology

authors： Hoque MA,Zhang Y,Chen L,Yang G,Khatun MA,Chen H,Hao L,Feng Y

更新日期：2017-05-19 00:00:00

abstract：:Enzymatic transfer of the AMP portion of ATP to substrate proteins has recently been described as an essential mechanism of bacterial infection for several pathogens. The first AMPylator to be discovered, VopS from Vibrio parahemolyticus, catalyzes the transfer of AMP onto the host GTPases Cdc42 and Rac1. Modification...

journal_title：ACS chemical biology

authors： Lewallen DM,Sreelatha A,Dharmarajan V,Madoux F,Chase P,Griffin PR,Orth K,Hodder P,Thompson PR

更新日期：2014-02-21 00:00:00

abstract：:Spinal muscular atrophy (SMA) is caused by deletion or mutation of both copies of the SMN1 gene, which produces an essential protein known as SMN. The severity of SMA is modified by variable copy number of a second gene,SMN2, which produces an mRNA that is incorrectly spliced with deletion of the last exon. We describ...

journal_title：ACS chemical biology

authors： Singh J,Salcius M,Liu SW,Staker BL,Mishra R,Thurmond J,Michaud G,Mattoon DR,Printen J,Christensen J,Bjornsson JM,Pollok BA,Kiledjian M,Stewart L,Jarecki J,Gurney ME

更新日期：2008-11-21 00:00:00

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

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

更新日期：2016-08-19 00:00:00