Diverse functional roles of reactive cysteines.

abstract：:Allosteric inhibitors can be more difficult to optimize without an understanding of how their binding influences the conformational motions of the target. Here, we used an integrated computational and experimental approach to probe the molecular mechanism of an allosteric inhibitor of heat shock protein 70 (Hsp70). Th...

journal_title：ACS chemical biology

authors： Rinaldi S,Assimon VA,Young ZT,Morra G,Shao H,Taylor IR,Gestwicki JE,Colombo G

更新日期：2018-11-16 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：:Gaussia luciferase (GLUC) is a bioluminescent reporter protein of increasing importance. As a secretory protein, it has increased sensitivity in vitro and in vivo (∼20 000-fold, and ∼1000-fold, respectively) over its competitor, secreted alkaline phosphatase. Unfortunately, this same advantageous secretory nature of G...

journal_title：ACS chemical biology

authors： Gaur S,Bhargava-Shah A,Hori S,Afjei R,Sekar TV,Gambhir SS,Massoud TF,Paulmurugan R

更新日期：2017-09-15 00:00:00

abstract：:Zinc plays both physiological and pathological roles in biology, making it of increasing interest. To date, intracellular free zinc has been measured in cell types supplemented with or enriched in zinc, such as hippocampal neurons. Here we quantitatively image intracellular exchangeable zinc in an ordinary resting cel...

journal_title：ACS chemical biology

authors： Bozym RA,Thompson RB,Stoddard AK,Fierke CA

更新日期：2006-03-17 00:00:00

abstract：:Originally discovered as part of an adaptive bacterial defense system against the invasion of foreign phages, programmable CRISPR-Cas nucleases have emerged as remarkable enzymes with transformative potential for both biological research and clinical application. CRISPR-Cas nucleases likely evolved in their natural co...

journal_title：ACS chemical biology

authors： Tsai SQ

更新日期：2018-02-16 00:00:00

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

authors： Nett RS,Contreras T,Peters RJ

更新日期：2017-04-21 00:00:00

abstract：:Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to sequestration of ...

journal_title：ACS chemical biology

authors： Khan E,Tawani A,Mishra SK,Verma AK,Upadhyay A,Kumar M,Sandhir R,Mishra A,Kumar A

更新日期：2018-01-19 00:00:00

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

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

更新日期：2016-08-19 00:00:00

abstract：:Secreted tyrosinase from melanin-forming Streptomyces avermitilis MA4680 was involved in both ortho-hydroxylation and further oxidation of trans-resveratrol, leading to the formation of melanin. This finding was confirmed by constructing deletion mutants of melC(2) and melD(2) encoding extracellular and intracellular ...

journal_title：ACS chemical biology

authors： Lee N,Kim EJ,Kim BG

更新日期：2012-10-19 00:00:00

abstract：:Caenorhabditis elegans lives in compost and decaying fruit, eats bacteria and is exposed to pathogenic microbes. We show that C. elegans is able to modify diverse microbial small-molecule toxins via both O- and N-glucosylation as well as unusual 3'-O-phosphorylation of the resulting glucosides. The resulting glucosyla...

journal_title：ACS chemical biology

authors： Stupp GS,von Reuss SH,Izrayelit Y,Ajredini R,Schroeder FC,Edison AS

更新日期：2013-02-15 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：: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：: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

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

更新日期：2016-01-15 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：:As part of the central core domain of the ribosome, helix 69 of 23S rRNA participates in an important intersubunit bridge and contacts several protein translation factors. Helix 69 is believed to play key roles in protein synthesis. Even though high-resolution crystal structures of the ribosome exist, the solution dyn...

journal_title：ACS chemical biology

authors： Sakakibara Y,Chow CS

更新日期：2012-05-18 00:00:00

abstract：:One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAF(V600) mutant melanomas. However, they paradoxically promote th...

journal_title：ACS chemical biology

authors： Molzan M,Kasper S,Röglin L,Skwarczynska M,Sassa T,Inoue T,Breitenbuecher F,Ohkanda J,Kato N,Schuler M,Ottmann C

更新日期：2013-09-20 00:00:00

abstract：:For the specificity of ALOX15 orthologs of different mammals, the geometry of the amino acids Phe353, Ile418, Met419, and Ile593 ("triad determinants") is important, and mutagenesis of these residues altered the reaction specificity of these enzymes. Here we expressed wild-type human ALOX5 and its F359W/A424I/N425M/A6...

journal_title：ACS chemical biology

authors： Ivanov I,Golovanov AB,Ferretti C,Canyelles-Niño M,Heydeck D,Stehling S,Lluch JM,González-Lafont À,Kühn H

更新日期：2019-12-20 00:00:00

abstract：:We recently reported two novel tools for precisely controlling and quantifying Cas9 activity: a chemically inducible Cas9 variant (ciCas9) that can be rapidly activated by small molecules and a ddPCR assay for time-resolved measurement of DNA double strand breaks (DSB-ddPCR). Here, we further demonstrate the potential...

journal_title：ACS chemical biology

authors： Rose JC,Stephany JJ,Wei CT,Fowler DM,Maly DJ

更新日期：2018-02-16 00:00:00

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

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

abstract：:Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology. Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conj...

journal_title：ACS chemical biology

authors： Qin K,Zhu Y,Qin W,Gao J,Shao X,Wang YL,Zhou W,Wang C,Chen X

更新日期：2018-08-17 00:00:00

abstract：:Complexity generation in naturally occurring peptide scaffolds can occur either by posttranslational modifications of nascent ribosomal proteins or through post assembly line tailoring of nonribosomal peptides. Short enzymatic pathways utilizing bimodular and trimodular nonribosomal peptide synthetase (NRPS) assembly ...

journal_title：ACS chemical biology

authors： Walsh CT,Haynes SW,Ames BD,Gao X,Tang Y

更新日期：2013-07-19 00:00:00

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：:Access to well-defined ubiquitin conjugates has been key to elucidating the biochemical functions of proteins in the ubiquitin signaling network. Yet, we have a poor understanding of how deubiquitinases and ubiquitin-binding proteins respond to ubiquitin modifications when anchored to a protein other than ubiquitin or...

journal_title：ACS chemical biology

authors： Chang LH,Strieter ER

更新日期：2018-09-21 00:00:00

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

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

更新日期：2016-04-15 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

abstract：:Signal transducer and activator of transcription (STAT) proteins have important biological functions; however, deregulation of STAT signaling is a driving force behind the onset and progression of inflammatory diseases and cancer. While their biological roles suggest that STAT proteins would be valuable targets for de...

journal_title：ACS chemical biology

authors： Attarha S,Reithmeier A,Busker S,Desroses M,Page BDG

更新日期：2020-07-17 00:00:00

abstract：:The epidermal growth-factor-like domain A (EGF-A) of the low-density lipoprotein (LDL) receptor is a promising lead for therapeutic inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9). However, the clinical potential of EGF-A is limited by its suboptimal affinity for PCSK9. Here, we use phage display t...

journal_title：ACS chemical biology

authors： Tombling BJ,Lammi C,Lawrence N,Li J,Arnoldi A,Craik DJ,Wang CK

更新日期：2021-01-29 00:00:00

abstract：:Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are critical to maintain genome integrity, in which the base excision repair pathway plays an essential role. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for removing the deaminated bases f...

journal_title：ACS chemical biology

authors： Zhang Z,Shen J,Yang Y,Li J,Cao W,Xie W

更新日期：2016-06-17 00:00:00

abstract：:There is a current and pressing need for improved cancer therapies. The use of small molecule kinase inhibitors and their application in combinatorial regimens represent an approach to personalized targeted cancer therapy. A number of AGC kinases, including atypical Protein Kinase C enzymes (PKCs), are validated drug ...

journal_title：ACS chemical biology

authors： Arencibia JM,Fröhner W,Krupa M,Pastor-Flores D,Merker P,Oellerich T,Neimanis S,Schmithals C,Köberle V,Süß E,Zeuzem S,Stark H,Piiper A,Odadzic D,Schulze JO,Biondi RM

更新日期：2017-02-17 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