Abstract:
:Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a multiplicity of histone modifications has some analogy with their role in enabling structural diversity in secondary metabolism.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Loenarz C,Schofield CJdoi
10.1038/nchembio0308-152subject
Has Abstractpub_date
2008-03-01 00:00:00pages
152-6issue
3eissn
1552-4450issn
1552-4469pii
nchembio0308-152journal_volume
4pub_type
杂志文章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::Oxidase and oxygenase enzymes allow the use of relatively unreactive O2 in biochemical reactions. Many of the mechanistic strategies used in nature for this key reaction are represented within the 2-histidine-1-carboxylate facial triad family of non-heme Fe(II)-containing enzymes. The open face of the metal coordinati...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.71
更新日期:2008-03-01 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::Kinetochores act as hubs for multiple activities during cell division, including microtubule interactions and spindle checkpoint signaling. Each kinetochore can act autonomously, and activities change rapidly as proteins are recruited to, or removed from, kinetochores. Understanding this dynamic system requires tools ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2456
更新日期:2017-10-01 00:00:00
abstract::The actin cytoskeleton supports diverse cellular processes such as endocytosis, oriented growth, adhesion and migration. The dynamic nature of the cytoskeleton, however, has made it difficult to define the roles of the many accessory molecules that modulate actin organization, especially the multifunctional adapter pr...
journal_title:Nature chemical biology
pub_type: 信件
doi:10.1038/nchembio755
更新日期:2006-01-01 00:00:00
abstract::Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although mo...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2459
更新日期:2017-10-01 00:00:00
abstract::Binding to the primary receptor, CD4, triggers conformational changes in the metastable HIV-1 envelope glycoprotein (Env) trimer ((gp120-gp41)3) that are important for virus entry into host cells. These changes include an 'opening' of the trimer, creation of a binding site for the CCR5 co-receptor and formation and/or...
journal_title:Nature chemical biology
pub_type: 杂志文章
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更新日期:2014-10-01 00:00:00
abstract::The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. I...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2168
更新日期:2016-11-01 00:00:00
abstract::Linking bioactive compounds to their cellular targets is a central challenge in chemical biology. Here we report the mode of action of theonellamides, bicyclic peptides derived from marine sponges. We generated a chemical-genomic profile of theonellamide F using a collection of fission yeast strains in which each open...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.387
更新日期:2010-07-01 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::Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense activator. Here we descr...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1520
更新日期:2014-06-01 00:00:00
abstract::Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.694
更新日期:2011-10-30 00:00:00
abstract::Methods to evolve synthetic, rather than biological, polymers could significantly expand the functional potential of polymers that emerge from in vitro evolution. Requirements for synthetic polymer evolution include (i) sequence-specific polymerization of synthetic building blocks on an amplifiable template, (ii) disp...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.280
更新日期:2010-02-01 00:00:00
abstract::Helical membrane proteins are typically assumed to attain stable transmembrane topologies immediately upon co-translational membrane insertion. Here we show that unassembled monomers of the small multidrug resistance (SMR) family exist in a dynamic equilibrium where the N-terminal transmembrane helix flips in and out ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0356-9
更新日期:2019-10-01 00:00:00
abstract::Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge. Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway constructi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1494
更新日期:2014-05-01 00:00:00
abstract::ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 uniqu...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2180
更新日期:2016-12-01 00:00:00
abstract::We describe Scaffold Hunter, a highly interactive computer-based tool for navigation in chemical space that fosters intuitive recognition of complex structural relationships associated with bioactivity. The program reads compound structures and bioactivity data, generates compound scaffolds, correlates them in a hiera...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.187
更新日期:2009-08-01 00:00:00
abstract::Small ubiquitin-like modifier (SUMO) family proteins regulate target-protein functions by post-translational modification. However, a potent and selective inhibitor targeting the SUMO pathway has been lacking. Here we describe ML-792, a mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in c...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2463
更新日期:2017-11-01 00:00:00
abstract::Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strate...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2489
更新日期:2017-12-01 00:00:00
abstract::Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivati...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0041-4
更新日期:2018-06-01 00:00:00
abstract::Identification of endogenous glycan-binding ligands for cell-surface receptors has been difficult. Incorporation of a photoactive sialic acid analog into B-cell surface glycoproteins suggests that CD22 molecules may cluster by binding carbohydrate antigens on neighboring CD22 molecules. ...
journal_title:Nature chemical biology
pub_type: 评论,新闻
doi:10.1038/nchembio0705-69
更新日期:2005-07-01 00:00:00
abstract::The discovery of functional RNAs that are critical for normal and disease physiology continues to expand at a breakneck pace. Many RNA functions are controlled by the formation of specific structures, and an understanding of each structural component is necessary to elucidate its function. Measuring solvent accessibil...
journal_title:Nature chemical biology
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
abstract::The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift...
journal_title:Nature chemical biology
pub_type: 杂志文章
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更新日期:2017-04-01 00:00:00
abstract::Methods for imaging and tracking single molecules conjugated with fluorescent probes, called single-molecule tracking (SMT), are now providing researchers with the unprecedented ability to directly observe molecular behaviors and interactions in living cells. Current SMT methods are achieving almost the ultimate spati...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.1558
更新日期:2014-07-01 00:00:00
abstract::Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a ge...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0085-5
更新日期:2018-09-01 00:00:00
abstract::MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR rel...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00667-5
更新日期:2021-01-01 00:00:00
abstract::To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0284-8
更新日期:2019-06-01 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::Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional mater...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0169-2
更新日期:2019-01-01 00:00:00
abstract::The catalytic versatility of cytochrome P450 monooxygenases is remarkable. Here, we present mechanistic and structural characterizations of TleB from Streptomyces blastmyceticus and its homolog HinD from Streptoalloteichus hindustanus, which catalyze unusual intramolecular C-N bond formation to generate indolactam V f...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0380-9
更新日期:2019-12-01 00:00:00