Abstract:
:What do organic synthesis, mechanistic enzymology, structural biology and glycoscience have in common? They all span chemistry and biology, benefit from and contribute to multidisciplinary approaches, and were up for discussion at a recent symposium in Dublin.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Murphy PV,Rutledge PJdoi
10.1038/nchembio0206-59keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
59-62issue
2eissn
1552-4450issn
1552-4469pii
nchembio0206-59journal_volume
2pub_type
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::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::The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as t...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0036-1
更新日期:2018-05-01 00:00:00
abstract::Here we identify the amino acid transporter AnsP1 as the unique aspartate importer in the human pathogen Mycobacterium tuberculosis. Metabolomic analysis of a mutant with an inactive AnsP1 revealed that the transporter is essential for M. tuberculosis to assimilate nitrogen from aspartate. Virulence of the AnsP1 mutan...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1355
更新日期:2013-11-01 00:00:00
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 mult...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0308-152
更新日期:2008-03-01 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::We report that simple glycoside donors can drastically shift the equilibria of glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an endothermic to an exothermic process. To demonstrate the utility of this thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed synthesis ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.638
更新日期:2011-08-21 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::Lysine riboswitches are bacterial RNA structures that sense the concentration of lysine and regulate the expression of lysine biosynthesis and transport genes. Members of this riboswitch class are found in the 5' untranslated region of messenger RNAs, where they form highly selective receptors for lysine. Lysine bindi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio842
更新日期:2007-01-01 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::In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNATrp) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2312
更新日期:2017-04-01 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::Glycosyltransferases are ubiquitous enzymes that catalyze the assembly of glycoconjugates throughout all kingdoms of nature. A long-standing problem is the rational design of probes that can be used to manipulate glycosyltransferase activity in cells and tissues. Here we describe the rational design and synthesis of a...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.520
更新日期:2011-03-01 00:00:00
abstract::CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human c...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2179
更新日期:2016-11-01 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::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::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::F(1)-ATPase is an ATP-driven rotary motor protein in which the γ-subunit rotates against the catalytic stator ring. Although the reaction scheme of F(1) has mostly been revealed, the timing of inorganic phosphate (P(i)) release remains controversial. Here we addressed this issue by verifying the reversibility of ATP h...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.443
更新日期:2010-11-01 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::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::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::Gut microbiota is found in virtually any metazoan, from invertebrates to vertebrates. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. However, the exact molecular relationship am...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.1535
更新日期:2014-06-01 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::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
doi:10.1038/nchembio.1404
更新日期:2014-02-01 00:00:00
abstract::Intracellular Ca(2+) regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a approximately 1-kDa biarsenical Ca(2+) indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca(2+)] su...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2007.4
更新日期:2007-07-01 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::AMPA receptors mediate fast excitatory neurotransmission by converting chemical signals into electrical signals, and thus it is important to understand the relationship between their chemical biology and their function. We used single-molecule fluorescence resonance energy transfer to examine the conformations explore...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.523
更新日期:2011-03-01 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::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::Regio- and stereospecific incorporation of a halogen atom to an unactivated sp(3) carbon in a freestanding molecule is a challenging transformation that is currently missing in the inventory of enzyme-mediated reactions. Here we report what is to our knowledge the first example of a nonheme iron enzyme (WelO5) in the ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1625
更新日期:2014-11-01 00:00:00