Abstract:
:Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. Chemical biologists could play a central role in this effort.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Edwards AM,Bountra C,Kerr DJ,Willson TMdoi
10.1038/nchembio0709-436subject
Has Abstractpub_date
2009-07-01 00:00:00pages
436-40issue
7eissn
1552-4450issn
1552-4469pii
nchembio0709-436journal_volume
5pub_type
杂志文章abstract::Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion. However, detailed studies of the m...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio768
更新日期:2006-03-01 00:00:00
abstract::Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1817
更新日期:2015-07-01 00:00:00
abstract::More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remai...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2127
更新日期:2016-09-01 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::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 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:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-019-0230-9
更新日期:2019-03-01 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::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::Sulfoquinovose is produced by photosynthetic organisms at a rate of 10(10) tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2023
更新日期:2016-04-01 00:00:00
abstract::Molecular dynamics are essential for protein function. In some cases these dynamics involve the interconversion between ground state, highly populated conformers and less populated higher energy structures ('excited states') that play critical roles in biochemical processes. Here we describe recent advances in NMR spe...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.238
更新日期:2009-11-01 00:00:00
abstract::Protein serine-threonine kinase casein kinase II (CK2) is involved in a myriad of cellular processes including cell growth and proliferation through its phosphorylation of hundreds of substrates, yet how CK2 function is regulated is poorly understood. Here we report that the CK2 catalytic subunit CK2α is modified by O...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.771
更新日期:2012-01-22 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::Only 25% of bacterial membrane transporters have functional annotation owing to the difficulty of experimental study and of accurate prediction of their function. Here we report a sequence-independent method for high-throughput mining of novel transporters. The method is based on ligand-responsive biosensor systems th...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2189
更新日期:2016-12-01 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::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::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::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::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::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::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
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::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
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_title:Nature chemical biology
pub_type:
doi:10.1038/nchembio0206-59
更新日期:2006-02-01 00:00:00
abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-018-0073-9
更新日期:2018-06-01 00:00:00
abstract::Thiazole/oxazole-modified microcins (TOMMs) encompass a recently defined class of ribosomally synthesized natural products with a diverse set of biological activities. Although TOMM biosynthesis has been investigated for over a decade, the mechanism of heterocycle formation by the synthetase enzymes remains poorly und...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.944
更新日期:2012-04-22 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::A required course in communication at the graduate school level may help cure the disorder of poor scientific writing. ...
journal_title:Nature chemical biology
pub_type: 社论
doi:10.1038/nchembio0906-443
更新日期:2006-09-01 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::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