Bacterial β-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2).

abstract：:Dihydrofolate reductase (DHFR) is a potential drug target for Trypanosoma brucei, a human parasite, which is the causative agent for African sleeping sickness. No drug is available against this target, since none of the classical antifolates such as pyrimethamine (PYR), cycloguanil, or trimethoprim are effective as se...

journal_title：ACS chemical biology

authors： Vanichtanankul J,Taweechai S,Yuvaniyama J,Vilaivan T,Chitnumsub P,Kamchonwongpaisan S,Yuthavong Y

更新日期：2011-09-16 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：: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：:Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by β-lactam antibiotics. We report herein our structural insights into catalysis by the essentia...

journal_title：ACS chemical biology

authors： Bernardo-García N,Mahasenan KV,Batuecas MT,Lee M,Hesek D,Petráčková D,Doubravová L,Branny P,Mobashery S,Hermoso JA

更新日期：2018-03-16 00:00:00

abstract：:Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell-permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of...

journal_title：ACS chemical biology

authors： Rzuczek SG,Gao Y,Tang ZZ,Thornton CA,Kodadek T,Disney MD

更新日期：2013-10-18 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：:Chloropupukeananin and chloropestolides are novel metabolites of the plant endophyte Pestalotiopsis fici, showing antimicrobial, antitumor, and anti-HIV activities. Their highly complex and unique skeletons were generated from the coisolated pestheic acid (1) and iso-A82775C (10) based on our previous studies. Here, w...

journal_title：ACS chemical biology

authors： Pan Y,Liu L,Guan F,Li E,Jin J,Li J,Che Y,Liu G

更新日期：2018-03-16 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：: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：:Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously b...

journal_title：ACS chemical biology

authors： Vitvitsky V,Miljkovic JL,Bostelaar T,Adhikari B,Yadav PK,Steiger AK,Torregrossa R,Pluth MD,Whiteman M,Banerjee R,Filipovic MR

更新日期：2018-08-17 00:00:00

abstract：:Methods for the rapid identification of defined cell growth conditions are lacking. This deficiency is a major barrier to the investigation and application of human embryonic stem (ES) cells. To address this problem, we developed a method for generating arrays of self-assembled monolayers (SAMs) in which each element ...

journal_title：ACS chemical biology

authors： Derda R,Li L,Orner BP,Lewis RL,Thomson JA,Kiessling LL

更新日期：2007-05-22 00:00:00

abstract：:The degree to which anticancer agents selectively target cancer cells is a key determinant in successful therapeutic outcomes. Inhibitors of the Hsp90 molecular chaperone represent an important new class of anticancer agents. We propose here a novel mechanism by which physiochemical properties of Hsp90 inhibitors can ...

journal_title：ACS chemical biology

authors： Duvvuri M,Konkar S,Hong KH,Blagg BS,Krise JP

更新日期：2006-06-20 00:00:00

abstract：:Ineffective cellular delivery is a common problem in numerous biological applications. Developing delivery reagents that work robustly in a variety of experimental settings remains a challenge. Herein, we report how peptides derived from the prototypical cell penetrating peptide TAT can be used in combination with a s...

journal_title：ACS chemical biology

authors： Allen J,Najjar K,Erazo-Oliveras A,Kondow-McConaghy HM,Brock DJ,Graham K,Hager EC,Marschall ALJ,Dübel S,Juliano RL,Pellois JP

更新日期：2019-12-20 00:00:00

abstract：:Enzymatic plasticity, as a modern term referring to the functional conversion of an enzyme, is significant for enzymatic activity redesign. The bacterial diterpene cyclase CotB2 is a typical plastic enzyme by which its native form precisely conducts a chemical reaction while its mutants diversify the catalytic functio...

journal_title：ACS chemical biology

authors： Tang X,Zhang F,Zeng T,Li W,Yin S,Wu R

更新日期：2020-10-16 00:00:00

abstract：:Chemical cross-linking is well-established for investigating protein-protein interactions. Traditionally, photo cross-linking is used but is associated with problems of selectivity and UV toxicity in a biological context. We here describe, with live cells and under normal growth conditions, selective cross-linking of ...

journal_title：ACS chemical biology

authors： Vannecke W,Ampe C,Van Troys M,Beltramo M,Madder A

更新日期：2017-08-18 00:00:00

abstract：:Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal ...

journal_title：ACS chemical biology

authors： Bassenden AV,Rodionov D,Shi K,Berghuis AM

更新日期：2016-05-20 00:00:00

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

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

更新日期：2020-03-20 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：:Insights into the thermodynamic and kinetic signature of the transient opening of a protein-binding pocket resulting from accommodation of suitable substituents attached to a given parent ligand scaffold are presented. As a target, we selected human aldose reductase, an enzyme involved in the development of late-stage...

journal_title：ACS chemical biology

authors： Rechlin C,Scheer F,Terwesten F,Wulsdorf T,Pol E,Fridh V,Toth P,Diederich WE,Heine A,Klebe G

更新日期：2017-05-19 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：:Engineering gene circuits with novel functions holds promise for broad applications in biology, engineering, and medicine. Directed evolution complements rational design as an important strategy for optimizing gene circuits and circuit elements. ...

journal_title：ACS chemical biology

authors： Song H,You L

更新日期：2006-12-20 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：:The endoplasmic reticulum (ER) is the initial site of biogenesis of secretory pathway proteins, including proteins localized to the ER, Golgi, lysosomes, intracellular vesicles, plasma membrane, and extracellular compartments. Proteins within the secretory pathway contain a high abundance of disulfide bonds to protect...

journal_title：ACS chemical biology

authors： Bechtel TJ,Li C,Kisty EA,Maurais AJ,Weerapana E

更新日期：2020-02-21 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：:Synthetic biology is the realization of systems with desired behavior using biological materials. A recent addition to the field is a bipartite consortium of the bacterium Escherichia coli in which each species harbors complementary gene circuits that actuate only when both are present above a critical density. This b...

journal_title：ACS chemical biology

authors： Wong JV,Song H,You L

更新日期：2008-01-18 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：:Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in a...

journal_title：ACS chemical biology

authors： Battersby BJ,Richter U,Safronov O

更新日期：2019-11-15 00:00:00

abstract：:Prenylated indole alkaloid okaramines selectively target insect glutamate-gated chloride channels (GluCls). Because of their highly complex structures, including azocine and azetidine rings, total synthesis of okaramine A or B has not been achieved, preventing evaluation of the biological activities of okaramines. Bio...

journal_title：ACS chemical biology

authors： Kato N,Furutani S,Otaka J,Noguchi A,Kinugasa K,Kai K,Hayashi H,Ihara M,Takahashi S,Matsuda K,Osada H

更新日期：2018-03-16 00:00:00

abstract：:Binding of the Fc domain of Immunoglobulin G (IgG) to Fcγ receptors on leukocytes can initiate a series of signaling events resulting in antibody-dependent cell-mediated cytotoxicity (ADCC) and other important immune responses. Fc domains lacking glycosylation at N297 have greatly diminished Fcγ receptor binding and l...

journal_title：ACS chemical biology

authors： Borrok MJ,Jung ST,Kang TH,Monzingo AF,Georgiou G

更新日期：2012-09-21 00:00:00

abstract：:The limited clinical success of therapeutics targeting cellular signaling processes is due to multiple factors, including off-target effects and complex feedback regulation encoded within the signaling network. To understand these effects, chemical proteomics and chemical genetics tools have been developed to map the ...

journal_title：ACS chemical biology

authors： Carlson SM,White FM

更新日期：2011-01-21 00:00:00