Abstract：
:The quest for ever more selective kinase inhibitors as potential future drugs has yielded a large repertoire of chemical probes that are selective for specific kinase conformations. These probes have been useful tools to obtain structural snapshots of kinase conformational plasticity. Similarly, kinetic and thermodynamic inhibitor binding experiments provide glimpses at the time scales and energetics of conformational interconversions. These experimental insights are complemented by computational predictions of conformational energy landscapes and simulations of conformational transitions and of the process of inhibitors binding to the protein kinase domain. A picture emerges in which highly selective inhibitors capitalize on the dynamic nature of kinases.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Tong M,Seeliger MAdoi
10.1021/cb500870asubject
Has Abstractpub_date
2015-01-16 00:00:00pages
190-200issue
1eissn
1554-8929issn
1554-8937journal_volume
10pub_type
杂志文章,评审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
pub_type： 杂志文章
doi：10.1021/acschembio.6b00431
更新日期：2016-08-19 00:00:00
abstract：:The molecular chaperone Hsp90 requires the assistance of immunophilins, co-chaperones, and partner proteins for the conformational maturation of client proteins. Hsp90 inhibition represents a promising anticancer strategy due to the dependence of numerous oncogenic signaling pathways upon Hsp90 function. Historically,...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb400906e
更新日期：2014-04-18 00:00:00
abstract：:Terpenes are ubiquitous natural chemicals with diverse biological functions spanning all three domains of life. In specialized metabolism, the active sites of terpene synthases (TPSs) evolve in shape and reactivity to direct the biosynthesis of a myriad of chemotypes for organismal fitness. As most terpene biosynthesi...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.5b00539
更新日期：2015-11-20 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
pub_type： 杂志文章
doi：10.1021/acschembio.0c00908
更新日期：2021-01-15 00:00:00
abstract：:RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb4001553
更新日期：2013-07-19 00:00:00
abstract：:Many pathogenic bacteria including Staphylococcus aureus use iron-chelating siderophores to acquire iron. Iron uptake oxidoreductase (IruO), a flavin adenine dinucleotide (FAD)-containing nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase from S. aureus, functions as a reductase for IsdG and IsdI,...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.7b00203
更新日期：2017-07-21 00:00:00
abstract：:X-ray crystallographic analysis of a bovine antibody (BLV1H12) revealed a unique scaffold in its ultralong heavy chain complementarity determining region 3 (CDR3H) that folds into a solvent exposed, antiparallel β-stranded "stalk" fused with a disulfide cross-linked "knob" domain. This unusual variable region motif pr...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb4004749
更新日期：2013-10-18 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
pub_type： 杂志文章
doi：10.1021/cb400088q
更新日期：2013-07-19 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
pub_type： 评论,杂志文章,评审
doi：10.1021/cb6004596
更新日期：2006-12-20 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb5002679
更新日期：2014-08-15 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb600393x
更新日期：2006-11-21 00:00:00
abstract：:Ammonia lyases catalyze the formation of α,β-unsaturated bonds by the elimination of ammonia from their substrates. This conceptually straightforward reaction has been the emphasis of many studies, with the main focus on the catalytic mechanism of these enzymes and/or the use of these enzymes as catalysts for the synt...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb3002792
更新日期：2012-10-19 00:00:00
abstract：:Hemolysis, a process by which the destruction of red blood cells leads to the release of hemoglobin, is a critical event observed during hemolytic disorders. Under oxidative stress conditions, hemoglobin can release its heme prosthetic group, which is highly cytotoxic and can catalyze the generation of reactive oxygen...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.8b00458
更新日期：2018-08-17 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章,评审
doi：10.1021/acschembio.9b00347
更新日期：2019-11-15 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
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journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00049
更新日期：2019-04-19 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章,评审
doi：10.1021/cb800138w
更新日期：2008-10-17 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb4008106
更新日期：2014-03-21 00:00:00
abstract：:Understanding the complex biochemical mechanisms that underlie the regulation, toxicity, and protein binding of metal ions requires the ability to analyze the metal content of individual proteins in complex mixtures. In this issue of ACS Chemical Biology, a technique combining gel electrophoresis with synchrotron X-ra...
journal_title：ACS chemical biology
pub_type： 评论,杂志文章
doi：10.1021/cb100145z
更新日期：2010-06-18 00:00:00
abstract：:Dicamba monooxygenase (DMO) catalyzes the O-demethylation of dicamba (3,6-dichloro-2-methoxybenzoate) to produce 3,6-dichlorosalicylate and formaldehyde. Recent crystallographic studies suggest that DMO catalyzes the challenging oxidation of a saturated C-H bond within the methyl group of dicamba to form a hemiacetal ...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb400154a
更新日期：2013-08-16 00:00:00
abstract：:Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, ...
journal_title：ACS chemical biology
pub_type： 杂志文章
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更新日期：2017-06-16 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章
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更新日期：2014-02-21 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章
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更新日期：2016-08-19 00:00:00
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journal_title：ACS chemical biology
pub_type： 杂志文章
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更新日期：2014-11-21 00:00:00
abstract：:Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyt...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb700159m
更新日期：2007-11-20 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
pub_type： 杂志文章
doi：10.1021/cb100094k
更新日期：2010-10-15 00:00:00
abstract：:Formylglycine (fGly) is a catalytically essential residue found almost exclusively in the active sites of type I sulfatases. Formed by post-translational oxidation of cysteine or serine side chains, this aldehyde-functionalized residue participates in a unique and highly efficient catalytic mechanism for sulfate ester...
journal_title：ACS chemical biology
pub_type： 杂志文章,评审
doi：10.1021/cb500897w
更新日期：2015-01-16 00:00:00
abstract：:The inhibitor of apoptosis (IAP) proteins are critical regulators of cancer cell survival, which makes them attractive targets for therapeutic intervention in cancers. Herein, we describe the structure-based design of IAP antagonists with high affinities and selectivity (>2000-fold) for c-IAP1 over XIAP and their func...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb900083m
更新日期：2009-07-17 00:00:00
abstract：:Angiogenesis, the formation of new blood vessels, is implicated in a number of important human diseases, including cancer, diabetic retinopathy, and rheumatoid arthritis. To identify clinically useful angiogenesis inhibitors, we assembled and screened a library of mostly Food and Drug Administration-approved drugs for...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb600362d
更新日期：2007-04-24 00:00:00
abstract：:Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation-in...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.6b00315
更新日期：2016-08-19 00:00:00
