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 brain.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Fischer PMdoi
10.1038/nchembio0808-448subject
Has Abstractpub_date
2008-08-01 00:00:00pages
448-9issue
8eissn
1552-4450issn
1552-4469pii
nchembio0808-448journal_volume
4pub_type
评论,杂志文章,评审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::We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpect...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.939
更新日期:2012-04-15 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::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 ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2116
更新日期:2016-09-01 00:00:00
abstract::Changes in the cellular environment modulate protein energy landscapes to drive important biology, with consequences for signaling, allostery and other vital processes. The effects of ubiquitination are particularly important because of their potential influence on degradation by the 26S proteasome. Moreover, proteaso...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0556-3
更新日期:2020-08-01 00:00:00
abstract::It is postulated that in addition to cell density, other factors such as the dimensions and diffusional characteristics of the environment could influence quorum sensing (QS) and induction of genetic reprogramming. Modeling studies predict that QS may operate at the level of a single cell, but, owing to experimental c...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.264
更新日期:2010-01-01 00:00:00
abstract::DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this reaction favors nucleotide incorporation, polymerases also catalyze a reverse reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates deoxynucleoside triphosphates. Because pyrophosphorolysis can influence polymeras...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2450
更新日期:2017-10-01 00:00:00
abstract::Hapalindole alkaloids are a structurally diverse class of cyanobacterial natural products defined by their varied polycyclic ring systems and diverse biological activities. These complex metabolites are generated from a common biosynthetic intermediate by the Stig cyclases in three mechanistic steps: a rare Cope rearr...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0003-x
更新日期:2018-04-01 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::Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2380
更新日期:2017-07-01 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::Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen-responsive i...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1793
更新日期:2015-05-01 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::Phenylketonuria (PKU) is characterized by phenylalanine accumulation and progressive mental retardation caused by an unknown mechanism. We demonstrate that at pathological concentrations, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These assemblies are ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1002
更新日期:2012-08-01 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::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::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::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::Nitrite represents a bioactive reservoir of nitric oxide (NO) that may modulate vasodilation, respiration and cytoprotection after ischemia-reperfusion injury. Although nitrite formation is thought to occur via reaction of NO with oxygen, this third-order reaction cannot compete kinetically with the reaction of NO wit...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio813
更新日期:2006-09-01 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::RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2132
更新日期:2016-09-01 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
pub_type: 杂志文章
doi:10.1038/nchembio.2537
更新日期:2018-02-01 00:00:00
abstract::Small molecules that specifically activate an intracellular protein of interest are highly desirable. A generally applicable strategy, however, remains elusive. Herein we describe a small molecule-triggered bioorthogonal protein decaging technique that relies on the inverse electron-demand Diels-Alder reaction for eli...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1656
更新日期:2014-12-01 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::Enzymes that use the cofactor thiamin diphosphate (ThDP, 1), the biologically active form of vitamin B(1), are involved in numerous metabolic pathways in all organisms. Although a theory of the cofactor's underlying reaction mechanism has been established over the last five decades, the three-dimensional structures of...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio788
更新日期:2006-06-01 00:00:00
abstract::The endocannabinoid 2-arachidonoylglycerol (2-AG) is biosynthesized by diacylglycerol lipases DAGLα and DAGLβ. Chemical probes to perturb DAGLs are needed to characterize endocannabinoid function in biological processes. Here we report a series of 1,2,3-triazole urea inhibitors, along with paired negative-control and ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1105
更新日期:2012-12-01 00:00:00
abstract::The ykkC family of bacterial riboswitches combines several widespread classes that have similar secondary structures and consensus motifs but control different genes in response to different cellular metabolites. Here we report the crystal structures of two distinct ykkC riboswitches specifically bound to their cognat...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0114-4
更新日期:2018-09-01 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 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::Secondary structure refolding is a key event in biology as it modulates the conformation of many proteins in the cell, generating functional or aberrant states. The crystal structures of mannosyltransferase PimA reveal an exceptional flexibility of the protein along the catalytic cycle, including β-strand-to-α-helix a...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1694
更新日期:2015-01-01 00:00:00