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 carbonate in the macrocyclic portion of cytochalasin E. This study expands the repertoire of activities of FMOs and provides a possible synthetic strategy for transformation of ketones into carbonates.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Hu Y,Dietrich D,Xu W,Patel A,Thuss JA,Wang J,Yin WB,Qiao K,Houk KN,Vederas JC,Tang Ydoi
10.1038/nchembio.1527subject
Has Abstractpub_date
2014-07-01 00:00:00pages
552-4issue
7eissn
1552-4450issn
1552-4469pii
nchembio.1527journal_volume
10pub_type
杂志文章abstract::Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalani...
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
abstract::Serine phosphorylation is a key post-translational modification that regulates diverse biological processes. Powerful analytical methods have identified thousands of phosphorylation sites, but many of their functions remain to be deciphered. A key to understanding the function of protein phosphorylation is access to p...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1823
更新日期:2015-07-01 00:00:00
abstract::Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1986
更新日期:2016-02-01 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::Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0496-y
更新日期:2020-05-01 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::Cell polarity is the asymmetric compartmentalization of cellular components. An opposing gradient of partitioning-defective protein kinases, atypical protein kinase C (aPKC) and PAR-1, at the cell cortex guides diverse asymmetries in the structure of metazoan cells, but the mechanism underlying their spatial patternin...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0117-1
更新日期:2018-10-01 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
pub_type: 杂志文章
doi:10.1038/nchembio856
更新日期:2007-02-01 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::Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1910
更新日期:2015-11-01 00:00:00
abstract::Virtually all cells in the body have an intracellular clockwork based on a negative feedback mechanism. The circadian timekeeping system in mammals is a hierarchical multi-oscillator network, with the suprachiasmatic nuclei (SCN) acting as the central pacemaker. The SCN synchronizes to daily light-dark cycles and coor...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.2007.37
更新日期:2007-10-01 00:00:00
abstract::The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable i...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio0606-284
更新日期:2006-06-01 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::Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding α-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1357
更新日期:2013-11-01 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
abstract::The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the i...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.521
更新日期:2011-03-01 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
pub_type: 杂志文章
doi:10.1038/s41589-019-0447-7
更新日期:2020-02-01 00:00:00
abstract::The inability of cells to properly fold, modify and assemble secretory and transmembrane proteins leads to accumulation of misfolded proteins in the endoplasmic reticulum (ER). Under these conditions of 'ER stress', cell survival depends on homeostatic benefits from an intracellular signaling pathway called the unfold...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.1664
更新日期:2014-11-01 00:00:00
abstract::Nature uses a variety of tools to mediate the flow of information in cells, many of which control distances between key biomacromolecules. Researchers have thus generated compounds whose activities stem from interactions with two (or more) proteins simultaneously. In this Perspective, we describe how these 'bifunction...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-020-0469-1
更新日期:2020-04-01 00:00:00
abstract::Liver X receptors (Lxrα and Lxrβ) are ligand-dependent nuclear receptors critical for ventral midbrain neurogenesis in vivo. However, no endogenous midbrain Lxr ligand has so far been identified. Here we used LC/MS and functional assays to identify cholic acid as a new Lxr ligand. Moreover, 24(S),25-epoxycholesterol (...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1156
更新日期:2013-02-01 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::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::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
doi:10.1038/nchembio.1931
更新日期:2015-11-01 00:00:00
abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-018-0174-5
更新日期:2018-12-01 00:00:00
abstract::The chemical species involved in H2S signaling remain elusive despite the profound and pleiotropic physiological effects elicited by this molecule. The dominant candidate mechanism for sulfide signaling is persulfidation of target proteins. However, the relatively poor reactivity of H2S toward oxidized thiols, such as...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1834
更新日期:2015-07-01 00:00:00
abstract::Phosphorylation and glycosylation of the tau protein, which is implicated in neurodegenerative diseases, are intimately linked. In vivo pharmacological inhibition of tau deglycosylation may be a new way to suppress abnormal tau phosphorylation, known to be involved in the formation of neurofibrillary tangles in the br...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章,评审
doi:10.1038/nchembio0808-448
更新日期:2008-08-01 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::Cell-permeable small molecules that inhibit their targets on fast timescales are powerful probes of cell-division mechanisms. Such inhibitors have been identified using phenotype-based screens with chemical libraries. However, the characteristics of compound libraries needed to effectively span cell-division phenotype...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio826
更新日期:2006-11-01 00:00:00
abstract::The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-β-lysine ((3S)-3,6-diaminohexanoic acid) oligopeptides as pendant chains. Here we describe three unusual nonribosomal peptide synthetases (NRPSs) involved in ST biosynthesis: ORF 5 (a stand-alone adenylation (A) domain), ORF 18 (containi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1040
更新日期:2012-09-01 00:00:00
abstract::We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative demethylation activity targeting the abundant N6-methyladenosine (m(6)A) residues in RNA in vitro. FTO knockdown with siRNA led to increased amounts of m(6)A in mRNA, whereas overexpression of FTO resulted in decreased amounts of...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.687
更新日期:2011-10-16 00:00:00