Abstract：
:Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-allostery' mutations that mimic the effects of ligand in driving protein conformation allowed crystallization of the partial agonist ligand WAY-169916 with both the canonical active and inactive conformations of the estrogen receptor. The intermediate transcriptional activity induced by WAY-169916 is associated with the ligand binding differently to the active and inactive conformations of the receptor. Analyses of a series of chemical derivatives demonstrated that altering the ensemble of ligand binding orientations changes signaling output. The coupling of different ligand binding orientations to distinct active and inactive protein conformations defines a new mechanism for titrating allosteric signaling activity.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Bruning JB,Parent AA,Gil G,Zhao M,Nowak J,Pace MC,Smith CL,Afonine PV,Adams PD,Katzenellenbogen JA,Nettles KWdoi
10.1038/nchembio.451subject
Has Abstractpub_date
2010-11-01 00:00:00pages
837-43issue
11eissn
1552-4450issn
1552-4469pii
nchembio.451journal_volume
6pub_type
杂志文章abstract：:Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1527
更新日期：2014-07-01 00:00:00
abstract：:Nitric oxide (NO) signaling through the formation of cGMP is well established; however, there seems to be an increasing role for cGMP-independent NO signaling. Although key molecular details remain unanswered, S-nitrosation represents an example of cGMP-independent NO signaling. This modification has garnered recent a...
journal_title：Nature chemical biology
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更新日期：2005-08-01 00:00:00
abstract：:In eukaryotes, cytosolic monothiol glutaredoxins are proteins implicated in intracellular iron trafficking and sensing via their bound [2Fe-2S] clusters. We define a new role of human cytosolic monothiol glutaredoxin-3 (GRX3) in transferring its [2Fe-2S] clusters to human anamorsin, a physical and functional protein p...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1892
更新日期：2015-10-01 00:00:00
abstract：: ...
journal_title：Nature chemical biology
pub_type： 评论,杂志文章
doi：10.1038/s41589-018-0199-9
更新日期：2019-01-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43). Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause di...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1563
更新日期：2014-08-01 00:00:00
abstract：:Kinase inhibitors are important cancer drugs, but they tend to display limited target specificity, and their target profiles are often challenging to rationalize in terms of molecular mechanism. Here we report that the clinical kinase inhibitor bosutinib recognizes its kinase targets by engaging a pair of conserved st...
journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2014-02-01 00:00:00
abstract：:Genetic screens in cultured human cells represent a powerful unbiased strategy to identify cellular pathways that determine drug efficacy, providing critical information for clinical development. We used insertional mutagenesis-based screens in haploid cells to identify genes required for the sensitivity to lasonolide...
journal_title：Nature chemical biology
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更新日期：2020-02-01 00:00:00
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journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.798
更新日期：2012-02-26 00:00:00
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journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2070
更新日期：2016-06-01 00:00:00
abstract：:The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshapi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-020-00653-x
更新日期：2021-01-01 00:00:00
abstract：:Gentamicin B (GB), a valuable starting material for the preparation of the semisynthetic aminoglycoside antibiotic isepamicin, is produced in trace amounts by the wild-type Micromonospora echinospora. Though the biosynthetic pathway to GB has remained obscure for decades, we have now identified three hidden pathways t...
journal_title：Nature chemical biology
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更新日期：2019-03-01 00:00:00
abstract：:The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks o...
journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2017-11-01 00:00:00
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journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2016-04-01 00:00:00
abstract：:We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.551
更新日期：2011-05-01 00:00:00
abstract：:Excessive aggregation of proteins has a major impact on cell fate and is a hallmark of amyloid diseases in humans. To resolve insoluble deposits and to maintain protein homeostasis, all cells use dedicated protein disaggregation, protein folding and protein degradation factors. Despite intense recent research, the und...
journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2015-11-01 00:00:00
abstract：:The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...
journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2017-06-01 00:00:00
abstract：:Proper gene expression is essential for the survival of every cell. Once thought to be a passive transporter of genetic information, RNA has recently emerged as a key player in nearly every pathway in the cell. A full description of its structure is critical to understanding RNA function. Decades of research have focu...
journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.1958
更新日期：2015-12-01 00:00:00
abstract：:Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome....
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2370
更新日期：2017-07-01 00:00:00
abstract：:Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses of more than 4,500 natural products. Halogenation of unactivated carbon centers in the biosyntheses of several compounds of nonribosomal peptide origin is carried out by a class of mononuclear nonheme iron enzymes that require alpha-keto...
journal_title：Nature chemical biology
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更新日期：2007-02-01 00:00:00
abstract：:Molecular dynamics are essential for protein function. In some cases these dynamics involve the interconversion between ground state, highly populated conformers and less populated higher energy structures ('excited states') that play critical roles in biochemical processes. Here we describe recent advances in NMR spe...
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更新日期：2009-11-01 00:00:00
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更新日期：2011-10-30 00:00:00
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journal_title：Nature chemical biology
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更新日期：2017-12-01 00:00:00
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journal_title：Nature chemical biology
pub_type： 杂志文章,评审
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更新日期：2018-02-14 00:00:00
abstract：:Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV c...
journal_title：Nature chemical biology
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更新日期：2018-02-01 00:00:00
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更新日期：2012-09-01 00:00:00
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journal_title：Nature chemical biology
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更新日期：2015-01-01 00:00:00
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journal_title：Nature chemical biology
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journal_title：Nature chemical biology
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更新日期：2018-10-01 00:00:00
abstract：:Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague, respectively, are pathogens with serious ongoing impact on global public health and potential use as agents of bioterrorism. Both pathogens have iron acquisition systems based on siderophores, secreted iron-chelating compo...
journal_title：Nature chemical biology
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更新日期：2005-06-01 00:00:00
