Thymoquinone blocks pSer/pThr recognition by Plk1 Polo-box domain as a phosphate mimic.

abstract：:Leishmaniases affect the poorest people on earth and have no effective drug therapy. Here, we present the crystal structure of the mitochondrial isoform of class I fumarate hydratase (FH) from Leishmania major and compare it to the previously determined cytosolic Leishmania major isoform. We further describe the mecha...

journal_title：ACS chemical biology

authors： Feliciano PR,Drennan CL,Nonato MC

更新日期：2019-02-15 00:00:00

abstract：:The cell utilizes the Keap1/Nrf2-ARE signaling pathway to detoxify harmful chemicals in order to protect itself from oxidative stress and to maintain its reducing environment. When exposed to oxidative stress and xenobiotic inducers, the redox sensitive Keap1 is covalently modified at specific cysteine residues. Conse...

journal_title：ACS chemical biology

authors： Wang R,Mason DE,Choe KP,Lewin AS,Peters EC,Luesch H

更新日期：2013-08-16 00:00:00

abstract：:In eukaryotic cells, proteins and RNAs are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably leptomycin B. However, up to now no small molecule inhibitors of nu...

journal_title：ACS chemical biology

authors： Hintersteiner M,Ambrus G,Bednenko J,Schmied M,Knox AJ,Meisner NC,Gstach H,Seifert JM,Singer EL,Gerace L,Auer M

更新日期：2010-10-15 00:00:00

abstract：:Bacteria harbor an immense reservoir of potentially new and therapeutic small molecules in the form of "silent" biosynthetic gene clusters (BGCs). These BGCs can be identified bioinformatically but are sparingly expressed under normal laboratory growth conditions, or not at all, and therefore do not produce significan...

journal_title：ACS chemical biology

authors： Moon K,Xu F,Zhang C,Seyedsayamdost MR

更新日期：2019-04-19 00:00:00

abstract：:Functionally selective ligands stabilize conformations of G protein-coupled receptors (GPCRs) that induce a preference for signaling via a subset of the intracellular pathways activated by the endogenous agonists. The possibility to fine-tune the functional activity of a receptor provides opportunities to develop drug...

journal_title：ACS chemical biology

authors： Männel B,Jaiteh M,Zeifman A,Randakova A,Möller D,Hübner H,Gmeiner P,Carlsson J

更新日期：2017-10-20 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：:Regulators of G protein signaling (RGS) proteins are key players in regulating signaling via G protein-coupled receptors. RGS proteins directly bind to the Gα-subunits of activated heterotrimeric G-proteins, and accelerate the rate of GTP hydrolysis, thereby rapidly deactivating G-proteins. Using atomistic simulations...

journal_title：ACS chemical biology

authors： Vashisth H,Storaska AJ,Neubig RR,Brooks CL 3rd

更新日期：2013-12-20 00:00:00

abstract：:Labeling of virus opens new pathways for the understanding of viruses themselves and facilitates the utilization of viruses in modern biology, medicine, and materials. Based on the characteristic that viruses hijack their host cellular machineries to survive and reproduce themselves, a host-cell-assisted strategy is p...

journal_title：ACS chemical biology

authors： Huang BH,Lin Y,Zhang ZL,Zhuan F,Liu AA,Xie M,Tian ZQ,Zhang Z,Wang H,Pang DW

更新日期：2012-04-20 00:00:00

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

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

abstract：:The complexity of the human proteome is greatly expanded by post-translational modifications. New tools capable of recognizing these modifications in a sequence-specific fashion provide a route to purify these modified proteins, to alter protein trafficking, and to visualize signal transduction in real time. Here, we ...

journal_title：ACS chemical biology

authors： Olson CA,Liao HI,Sun R,Roberts RW

更新日期：2008-08-15 00:00:00

abstract：:The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, ...

journal_title：ACS chemical biology

authors： Chowdhury R,Candela-Lena JI,Chan MC,Greenald DJ,Yeoh KK,Tian YM,McDonough MA,Tumber A,Rose NR,Conejo-Garcia A,Demetriades M,Mathavan S,Kawamura A,Lee MK,van Eeden F,Pugh CW,Ratcliffe PJ,Schofield CJ

更新日期：2013-07-19 00:00:00

abstract：:New machine learning methods to analyze raw chemical and biological data are now widely accessible as open-source toolkits. This positions researchers to leverage powerful, predictive models in their own domains. We caution, however, that the application of machine learning to experimental research merits careful cons...

journal_title：ACS chemical biology

authors： Chuang KV,Keiser MJ

更新日期：2018-10-19 00:00:00

abstract：:The steady increase in the prevalence of multidrug-resistant Staphylococcus aureus has made the search for novel antibiotics to combat this clinically important pathogen an urgent matter. In an effort to discover antibacterials with new chemical structures and mechanisms, we performed a growth inhibition screen of a s...

journal_title：ACS chemical biology

authors： Wang J,Ye X,Yang X,Cai Y,Wang S,Tang J,Sachdeva M,Qian Y,Hu W,Leeds JA,Yuan Y

更新日期：2020-07-17 00:00:00

abstract：:A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is ...

journal_title：ACS chemical biology

authors： Yang YL,Lee YP,Yang YL,Lin PC

更新日期：2014-02-21 00:00:00

abstract：:Although peptide-based reporters of protein tyrosine kinase (PTK) activity have been used to study PTK enzymology in vitro, the application of these reporters to intracellular conditions is compromised by their dephosphorylation, preventing PTK activity measurements. Nonproteinogenic amino acids may be utilized to rat...

journal_title：ACS chemical biology

authors： Turner AH,Lebhar MS,Proctor A,Wang Q,Lawrence DS,Allbritton NL

更新日期：2016-02-19 00:00:00

abstract：:The goal of incorporating renewable carbon into the fuel and chemical enterprise will most likely be successful when combined systems of biocatalysts and chemical catalysts are exploited. Significant efforts in the biocatalytic release of sugars from biomass are being pursued for subsequent use in fermentation. Two re...

journal_title：ACS chemical biology

authors： Shanks BH

更新日期：2007-08-17 00:00:00

abstract：:Generating highly selective probes to interrogate protein kinase function in biological studies remains a challenge, and new strategies are required. Herein, we describe the development of the first highly selective and cell-permeable inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves extensio...

journal_title：ACS chemical biology

authors： Brandvold KR,Steffey ME,Fox CC,Soellner MB

更新日期：2012-08-17 00:00:00

abstract：:Despite the stereospecificity of translation for l-amino acids (l-AAs) in vivo, synthetic biologists have enabled ribosomal incorporation of d-AAs in vitro toward encoding polypeptides with pharmacologically desirable properties. However, the steps in translation limiting d-AA incorporation need clarification. In this...

journal_title：ACS chemical biology

authors： Liljeruhm J,Wang J,Kwiatkowski M,Sabari S,Forster AC

更新日期：2019-02-15 00:00:00

abstract：:miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have d...

journal_title：ACS chemical biology

authors： Bose D,Jayaraj GG,Kumar S,Maiti S

更新日期：2013-05-17 00:00:00

abstract：:Histone post-translational modifications (PTMs) are crucial for many cellular processes including mitosis, transcription, and DNA repair. The cellular readout of histone PTMs is dependent on both the chemical modification and histone site, and the array of histone PTMs on chromatin is dynamic throughout the eukaryotic...

journal_title：ACS chemical biology

authors： Albanese KI,Krone MW,Petell CJ,Parker MM,Strahl BD,Brustad EM,Waters ML

更新日期：2020-01-17 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：:Recent advances in understanding the relevance of noncoding RNA (ncRNA) to disease have increased interest in drugging ncRNA with small molecules. The recent discovery of ribocil, a structurally distinct synthetic mimic of the natural ligand of the flavin mononucleotide (FMN) riboswitch, has revealed the potential che...

journal_title：ACS chemical biology

authors： Rizvi NF,Howe JA,Nahvi A,Klein DJ,Fischmann TO,Kim HY,McCoy MA,Walker SS,Hruza A,Richards MP,Chamberlin C,Saradjian P,Butko MT,Mercado G,Burchard J,Strickland C,Dandliker PJ,Smith GF,Nickbarg EB

更新日期：2018-03-16 00:00:00

abstract：:How primitive enzymes emerged from a primordial pool remains a fundamental unanswered question with important practical implications in synthetic biology. Here we show that a de novo evolved ATP binding protein, selected solely on the basis of its ability to bind ATP, mediates the regiospecific hydrolysis of ATP to AD...

journal_title：ACS chemical biology

authors： Simmons CR,Stomel JM,McConnell MD,Smith DA,Watkins JL,Allen JP,Chaput JC

更新日期：2009-08-21 00:00:00

abstract：:Current therapeutic interventions for both heart disease and heart failure are largely insufficient and associated with undesired side effects. Biomedical research has emphasized the role of sarcomeric protein function for the normal performance and energy efficiency of the heart, suggesting that directly targeting th...

journal_title：ACS chemical biology

authors： Parijat P,Kondacs L,Alexandrovich A,Gautel M,Cobb AJA,Kampourakis T

更新日期：2021-01-15 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：:Beta-peptides (beta-amino acid oligomers) that mimic the amphiphilic, helical, and cationic properties of natural antimicrobial peptides have previously been shown to display antifungal activity against planktonic Candida albicans cells. Beta-peptides offer several advantages over conventional peptides composed of alp...

journal_title：ACS chemical biology

authors： Karlsson AJ,Pomerantz WC,Neilsen KJ,Gellman SH,Palecek SP

更新日期：2009-07-17 00:00:00

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

authors： Bliska JB

更新日期：2006-07-21 00:00:00

abstract：:RNA methyltransferases (RNMTs) play important roles in RNA stability, splicing, and epigenetic mechanisms. They constitute a promising target class that is underexplored by the medicinal chemistry community. Information of relevance to drug design can be extracted from the rich structural coverage of human RNMTs. In t...

journal_title：ACS chemical biology

authors： Schapira M

更新日期：2016-03-18 00:00:00

abstract：:Histo-blood group epitopes are fucosylated branched oligosaccharides with well-defined conformations in solution that are recognized by receptors, such as lectins from pathogens. We report here the results of a series of experimental and computational endeavors revealing the unusual distortion of histo-blood group ant...

journal_title：ACS chemical biology

authors： Topin J,Lelimousin M,Arnaud J,Audfray A,Pérez S,Varrot A,Imberty A

更新日期：2016-07-15 00:00:00