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 from GluCl to mammalian Cys-loop receptors such as nicotinic acetylcholine and GABA receptors, it is important to ensure that established functional features of mammalian Cys-loop receptors are present in the more distantly related GluCl receptors. Here, we seek to identify ligand-binding interactions that are generally associated with Cys-loop receptors, including the frequently observed cation-π interaction. Our studies were performed on the highly homologous GluClβ receptor, because GluClα is not activated by glutamate in Xenopus laevis oocytes. Mutagenesis of the signal peptide and pore lining helix was performed to enhance functional expression and sensitivity to applied ligand, respectively. Conventional and unnatural amino acid mutagenesis indicate a strong cation-π interaction between Y206 and the protonated amine of glutamate, as well as other important ionic and hydrogen bond interactions between the ligand and the binding site, consistent with the crystal structure.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Daeffler KN,Lester HA,Dougherty DAdoi
10.1021/cb500323dsubject
Has Abstractpub_date
2014-10-17 00:00:00pages
2283-90issue
10eissn
1554-8929issn
1554-8937journal_volume
9pub_type
杂志文章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
pub_type: 杂志文章
doi:10.1021/cb7001522
更新日期:2007-08-17 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
pub_type: 杂志文章
doi:10.1021/cb500327m
更新日期:2014-10-17 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
pub_type: 杂志文章
doi:10.1021/acschembio.6b00081
更新日期:2016-04-15 00:00:00
abstract::RNAs are involved in interaction networks with other biomolecules and are crucial for proper cell function. Yet their biochemical analysis remains challenging. For Förster Resonance Energy Transfer (FRET), a common tool to study such interaction networks, two interacting molecules have to be fluorescently labeled. "Sp...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00332
更新日期:2017-12-15 00:00:00
abstract::Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes and are emerging as pioneering drug targets. Herein, we present a novel probe, Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling ide...
journal_title:ACS chemical biology
pub_type: 信件
doi:10.1021/acschembio.6b00766
更新日期:2016-12-16 00:00:00
abstract::Recent studies have shown that cholesterol plays a significant role in the ability of Toxin A from Clostridium difficile to enter eukaryotic cells. The translocation process is one of three major steps during intoxication that could be targeted for intervention against the severe antibiotic-associated diarrhea caused ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb600133b
更新日期:2006-04-25 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
pub_type: 杂志文章
doi:10.1021/acschembio.9b00476
更新日期:2019-12-20 00:00:00
abstract::Cell-penetrating peptides (CPPs) are capable of delivering membrane-impermeable cargoes (including small molecules, peptides, proteins, nucleic acids, and nanoparticles) into the cytosol of mammalian cells and have the potential to revolutionize biomedical research and drug discovery. However, the mechanism of action ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00478
更新日期:2020-09-18 00:00:00
abstract::Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and str...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00118
更新日期:2017-04-21 00:00:00
abstract::Changes in glycosylation are correlated to disease and associated with differentiation processes. Experimental tools are needed to investigate the physiological implications of these changes either by labeling of the modified glycans or by blocking their biosynthesis. N-Acetylgalactosamine (GalNAc) is a monosaccharide...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200511t
更新日期:2012-04-20 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
pub_type: 杂志文章
doi:10.1021/cb900093r
更新日期:2009-07-17 00:00:00
abstract::Lipopolysaccharide (LPS) is a crucial component in the outer membrane of Gram-negative bacteria that contributes to both pathogenicity as well as immunity against pathogenic bacteria. Typical LPS contains GlcN disaccharide as the core of lipid A. However, some bacteria such as Acidithiobacillus ferrooxidans and Leptos...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00791
更新日期:2020-12-18 00:00:00
abstract::Small molecule kinase inhibitors that stabilize distinct ATP binding site conformations can differentially modulate the global conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP binding site contacts are responsible for modulating the global conformation of SFKs and whether these inhi...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00429
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
pub_type: 杂志文章
doi:10.1021/cb400631w
更新日期:2014-02-21 00:00:00
abstract::The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their effi...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00256
更新日期:2017-08-18 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
pub_type: 杂志文章
doi:10.1021/cb700256w
更新日期:2008-01-18 00:00:00
abstract::Rediscovery of known compounds and time consumed in identification, especially high molecular weight compounds with complex structure, have let down interest in drug discovery. In this study, whole-genome analysis of microbe and Global Natural Products Social (GNPS) molecular networking helped in initial understanding...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00026
更新日期:2020-03-20 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
pub_type: 杂志文章
doi:10.1021/acschembio.7b00652
更新日期:2018-02-16 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
pub_type: 杂志文章,评审
doi:10.1021/cb500695k
更新日期:2014-12-19 00:00:00
abstract::Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Ther...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00700
更新日期:2020-11-20 00:00:00
abstract::The Akt kinase family, consisting of three isoforms in humans, is a well-validated class of drug target. Through various screening campaigns in academics and pharmaceutical industries, several promising inhibitors have been developed to date. However, due to the mechanistic and structural similarities of Akt kinases, ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200388k
更新日期:2012-03-16 00:00:00
abstract::There is increasing concern that animal and human reproduction may be adversely affected by exposure to xenoestrogens that activate estrogen receptors. There is evidence that one such compound, Bisphenol A (BPA), also induces meiotic and mitotic aneuploidy, suggesting that these kinds of molecules may also have effect...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb700210u
更新日期:2008-03-20 00:00:00
abstract::Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epig...
journal_title:ACS chemical biology
pub_type: 信件
doi:10.1021/acschembio.6b00627
更新日期:2016-12-16 00:00:00
abstract::APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200440y
更新日期:2012-03-16 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
pub_type: 杂志文章
doi:10.1021/acschembio.6b00827
更新日期:2017-02-17 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
pub_type: 杂志文章
doi:10.1021/acschembio.0c00809
更新日期:2021-01-15 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
pub_type: 杂志文章
doi:10.1021/acschembio.5b00109
更新日期:2015-07-17 00:00:00
abstract::C-methylation of aromatic small molecules by C-methyltransferases (C-MTs) is an important biological transformation that involves C-C bond formation using S-adenosyl-l-methionine (SAM) as the methyl donor. Here, two advances in the mechanistic understanding of C-methylation of the 8-position of coumarin substrates cat...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b01053
更新日期:2017-02-17 00:00:00
abstract::The past several years have seen numerous reports of new chemical modifications for use in RNA. In addition, in that time period, we have seen the discovery of several previously unknown naturally occurring modifications that impart novel properties on the parent RNAs. In this review, we describe recent discoveries in...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb200422t
更新日期:2012-01-20 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
pub_type: 杂志文章
doi:10.1021/acschembio.0c00645
更新日期:2020-10-16 00:00:00