Abstract:
:Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the aminonucleoside puromycin. Puromycin leaves a permanent and dose-dependent mark on treated cells that can be detected with high sensitivity and precision using a high-content, plate-based immunofluorescence assay. Using this new probe and screening approach, we detected alteration of cellular labile Fe(II) in response extracellular iron conditioning, overexpression of iron storage and/or export proteins, and post-translational regulation of iron export. We also used this new tool to demonstrate that labile Fe(II) pools are larger in cancer cells than in nontumorigenic cells.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Spangler B,Morgan CW,Fontaine SD,Vander Wal MN,Chang CJ,Wells JA,Renslo ARdoi
10.1038/nchembio.2116subject
Has Abstractpub_date
2016-09-01 00:00:00pages
680-5issue
9eissn
1552-4450issn
1552-4469pii
nchembio.2116journal_volume
12pub_type
杂志文章abstract::The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0250-5
更新日期:2019-05-01 00:00:00
abstract::Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00703-4
更新日期:2021-01-04 00:00:00
abstract::N(1)-Methyladenosine (m(1)A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topology and dynamics in mRNA. Here, we show that m(1)A is prevalent in Homo sapiens mRNA, which shows an m(1)A/A ratio of ∼0.02%. We develop the m(1)A-ID-seq technique, based on m(1)A immunoprec...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2040
更新日期:2016-05-01 00:00:00
abstract::Transcription factors have diverse roles during embryonic development, combinatorially controlling cellular states in a spatially and temporally defined manner. Resolving the dynamic transcriptional profiles that underlie these patterning processes is essential for understanding embryogenesis at the molecular level. H...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.772
更新日期:2012-01-29 00:00:00
abstract::The sea lamprey is an ancient, parasitic fish that invaded the Great Lakes a century ago, where it triggered the collapse of many fisheries. Like many fishes, this species relies on chemical cues to mediate key aspects of its life, including migration and reproduction. Here we report the discovery of a multicomponent ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio739
更新日期:2005-11-01 00:00:00
abstract::5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1848
更新日期:2015-08-01 00:00:00
abstract::The chemical scaffolds from which screening libraries are built have strong influence on the libraries' utility for screening campaigns. Here we present analysis of the scaffold composition of several types of commercially available screening collections and compare those compositions to those of drugs and drug candid...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0807-442
更新日期:2007-08-01 00:00:00
abstract::The lasso peptide microcin J25 is known to hijack the siderophore receptor FhuA for initiating internalization. Here, we provide what is to our knowledge the first structural evidence on the recognition mechanism, and our biochemical data show that another closely related lasso peptide cannot interact with FhuA. Our w...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1499
更新日期:2014-05-01 00:00:00
abstract::Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). We found ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.304
更新日期:2010-03-01 00:00:00
abstract::SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1593
更新日期:2014-09-01 00:00:00
abstract::Higher plants resist the forces of gravity and powerful lateral forces through the cumulative strength of the walls that surround individual cells. These walls consist mainly of cellulose, noncellulosic polysaccharides and lignin, in proportions that depend upon the specific functions of the cell and its stage of deve...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.439
更新日期:2010-10-01 00:00:00
abstract::Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry and the biological sciences. Metal ions function in numerous metalloenzymes, are incorporated into pharmaceuticals and imaging agents, and inspire the synthesis of catalysts used to achieve many chemical transformations. ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio1006-504
更新日期:2006-10-01 00:00:00
abstract::Post-transcriptional RNA modifications can be dynamic and might have functions beyond fine-tuning the structure and function of RNA. Understanding these RNA modification pathways and their functions may allow researchers to identify new layers of gene regulation at the RNA level. ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.482
更新日期:2010-12-01 00:00:00
abstract::The molecular forces that drive structural transitions between the open and closed states of channels and transporters are not well understood. The gate of the OmpA channel is formed by the central Glu52-Arg138 salt bridge, which can open to form alternate ion pairs with Lys82 and Glu128. To gain deeper insight into t...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio827
更新日期:2006-11-01 00:00:00
abstract::Actin filament dynamics are critical in cell motility. The structure of actin filament changes spontaneously and can also be regulated by actin-binding proteins, allowing actin to readily function in response to external stimuli. The interaction with the motor protein myosin changes the dynamic nature of actin filamen...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio763
更新日期:2006-02-01 00:00:00
abstract::Plants have recently moved into the spotlight owing to the growing realization that the world needs solutions to energy and food production that are sustainable and environmentally sound. Iron, copper and zinc are essential for plant growth and development, yet the same properties that make these transition metals ind...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.166
更新日期:2009-05-01 00:00:00
abstract::We report a salvage pathway in Gram-negative bacteria that bypasses de novo biosynthesis of UDP N-acetylmuramic acid (UDP-MurNAc), the first committed peptidoglycan precursor, and thus provides a rationale for intrinsic fosfomycin resistance. The anomeric sugar kinase AmgK and the MurNAc α-1-phosphate uridylyl transfe...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1289
更新日期:2013-08-01 00:00:00
abstract::ADP-ribosylation is a post-translational modification that is known to be involved in cellular homeostasis and stress but has been challenging to analyze biochemically. To facilitate the detection of ADP-ribosylated proteins, we show that an alkyne-adenosine analog, N6-propargyl adenosine (N6pA), is metabolically inco...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2280
更新日期:2017-03-01 00:00:00
abstract::Inorganic nitrite (NO(2)(-)) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO(3)(-)) is generally considered to be biologically inert. Bacteria express nitrate reductases that produce nitrite, but mammals lack these specific enzymes. Here...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.92
更新日期:2008-07-01 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::Signal transduction, regulatory processes and pharmaceutical responses are highly dependent upon ligand residence times. Gaining insight into how physical factors influence residence times (1/k(off)) should enhance our ability to manipulate biological interactions. We report experiments that yield structural insight i...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.769
更新日期:2012-01-15 00:00:00
abstract::The eukaryotic replicative DNA polymerases (Pol α, δ and ɛ) and the major DNA mutagenesis enzyme Pol ζ contain two conserved cysteine-rich metal-binding motifs (CysA and CysB) in the C-terminal domain (CTD) of their catalytic subunits. Here we demonstrate by in vivo and in vitro approaches the presence of an essential...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.721
更新日期:2011-11-27 00:00:00
abstract::Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoy...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2262
更新日期:2017-02-01 00:00:00
abstract::Regulation of gene expression in response to the changing environment is critical for cell survival. For instance, binding of macrolide antibiotics to the ribosome promotes translation arrest at the leader open reading frames ermCL and ermBL, which is necessary for inducing the antibiotic resistance genes ermC and erm...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1998
更新日期:2016-03-01 00:00:00
abstract::Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet the details of its spatial coordination are obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2060
更新日期:2016-06-01 00:00:00
abstract::Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed ma...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2268
更新日期:2017-03-01 00:00:00
abstract::BCL-2 family protein interactions regulate apoptosis, a critical process that maintains tissue homeostasis but can cause a host of human diseases when deregulated. Venetoclax is the first FDA-approved drug to reactivate apoptosis in cancer by selectively targeting an anti-apoptotic BCL-2 family member. The drug's acti...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-019-0306-6
更新日期:2019-07-01 00:00:00
abstract::The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of class I and II histone deacetylases (HDACs) as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.313
更新日期:2010-03-01 00:00:00
abstract::Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system....
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2417
更新日期:2017-09-01 00:00:00
abstract::RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-su...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2228
更新日期:2017-01-01 00:00:00