Light-activated chemical probing of nucleobase solvent accessibility inside cells.

abstract：:Gentamicin B (GB), a valuable starting material for the preparation of the semisynthetic aminoglycoside antibiotic isepamicin, is produced in trace amounts by the wild-type Micromonospora echinospora. Though the biosynthetic pathway to GB has remained obscure for decades, we have now identified three hidden pathways t...

journal_title：Nature chemical biology

authors： Ban YH,Song MC,Hwang JY,Shin HL,Kim HJ,Hong SK,Lee NJ,Park JW,Cha SS,Liu HW,Yoon YJ

更新日期：2019-03-01 00:00:00

abstract：:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43). Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause di...

journal_title：Nature chemical biology

authors： Barmada SJ,Serio A,Arjun A,Bilican B,Daub A,Ando DM,Tsvetkov A,Pleiss M,Li X,Peisach D,Shaw C,Chandran S,Finkbeiner S

更新日期：2014-08-01 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

authors： Dubey R,Stivala CE,Nguyen HQ,Goo YH,Paul A,Carette JE,Trost BM,Rohatgi R

更新日期：2020-02-01 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

authors： Dong C,Zhang H,Li L,Tempel W,Loppnau P,Min J

更新日期：2018-05-01 00:00:00

abstract：:Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of AD...

journal_title：Nature chemical biology

authors： Tsui CK,Barfield RM,Fischer CR,Morgens DW,Li A,Smith BAH,Gray MA,Bertozzi CR,Rabuka D,Bassik MC

更新日期：2019-10-01 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

authors： Xiao T,Frey G,Fu Q,Lavine CL,Scott DA,Seaman MS,Chou JJ,Chen B

更新日期：2020-05-01 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

authors： Loenarz C,Schofield CJ

更新日期：2008-03-01 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

authors： Baisden JT,Boyer JA,Zhao B,Hammond SM,Zhang Q

更新日期：2021-01-01 00:00:00

abstract：:We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...

journal_title：Nature chemical biology

authors： Lingwood D,Binnington B,Róg T,Vattulainen I,Grzybek M,Coskun U,Lingwood CA,Simons K

更新日期：2011-05-01 00:00:00

abstract：:Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C...

journal_title：Nature chemical biology

authors： Yan X,Wang X,Li Y,Zhou M,Li Y,Song L,Mi W,Min J,Dong C

更新日期：2021-01-04 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

authors： Liu AC,Lewis WG,Kay SA

更新日期：2007-10-01 00:00:00

abstract：:Many protein kinases are key nodal signaling molecules that regulate a wide range of cellular functions. These functions may require complex spatiotemporal regulation of kinase activities. Here, we show that protein kinase A (PKA), Ca(2+) and cyclic AMP (cAMP) oscillate in sync in insulin-secreting MIN6 beta cells, fo...

journal_title：Nature chemical biology

authors： Ni Q,Ganesan A,Aye-Han NN,Gao X,Allen MD,Levchenko A,Zhang J

更新日期：2011-01-01 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

authors： Bradshaw JM,McFarland JM,Paavilainen VO,Bisconte A,Tam D,Phan VT,Romanov S,Finkle D,Shu J,Patel V,Ton T,Li X,Loughhead DG,Nunn PA,Karr DE,Gerritsen ME,Funk JO,Owens TD,Verner E,Brameld KA,Hill RJ,Goldstein DM,

更新日期：2015-07-01 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

authors： Watanabe R,Iino R,Noji H

更新日期：2010-11-01 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

authors： Peters U,Cherian J,Kim JH,Kwok BH,Kapoor TM

更新日期：2006-11-01 00:00:00

abstract：:Serine is both a proteinogenic amino acid and the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. In the canonical pathway of glucose-derived serine synthesis, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step. Genetic loss of PHGDH is tox...

journal_title：Nature chemical biology

authors： Pacold ME,Brimacombe KR,Chan SH,Rohde JM,Lewis CA,Swier LJ,Possemato R,Chen WW,Sullivan LB,Fiske BP,Cho S,Freinkman E,Birsoy K,Abu-Remaileh M,Shaul YD,Liu CM,Zhou M,Koh MJ,Chung H,Davidson SM,Luengo A,Wang AQ,

更新日期：2016-06-01 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

authors： Lee WJ,Hase K

更新日期：2014-06-01 00:00:00

abstract：:Clinically significant antibiotic resistance has evolved against virtually every antibiotic deployed. Yet the development of new classes of antibiotics has lagged far behind our growing need for such drugs. Rather than focusing on therapeutics that target in vitro viability, much like conventional antibiotics, an alte...

journal_title：Nature chemical biology

authors： Clatworthy AE,Pierson E,Hung DT

更新日期：2007-09-01 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

authors： Maruyama C,Toyoda J,Kato Y,Izumikawa M,Takagi M,Shin-ya K,Katano H,Utagawa T,Hamano Y

更新日期：2012-09-01 00:00:00

abstract：:The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three ...

journal_title：Nature chemical biology

authors： Exell JC,Thompson MJ,Finger LD,Shaw SJ,Debreczeni J,Ward TA,McWhirter C,Siöberg CL,Martinez Molina D,Abbott WM,Jones CD,Nissink JW,Durant ST,Grasby JA

更新日期：2016-10-01 00:00:00

abstract：:Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, ...

journal_title：Nature chemical biology

authors： Rzuczek SG,Colgan LA,Nakai Y,Cameron MD,Furling D,Yasuda R,Disney MD

更新日期：2017-02-01 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

authors： Ogura Y,Parsons WH,Kamat SS,Cravatt BF

更新日期：2016-09-01 00:00:00

abstract：:The chemical scaffolds from which screening libraries are built have strong influence on the libraries' utility for screening campaigns. Here we present analysis of the scaffold composition of several types of commercially available screening collections and compare those compositions to those of drugs and drug candid...

journal_title：Nature chemical biology

authors： Shelat AA,Guy RK

更新日期：2007-08-01 00:00:00

abstract：:Methylation of nucleotides in ribosomal RNAs (rRNAs) is a ubiquitous feature that occurs in all living organisms. Identification of all enzymes responsible for rRNA methylation, as well as mapping of all modified rRNA residues, is now complete for a number of model species, such as Escherichia coli and Saccharomyces c...

journal_title：Nature chemical biology

authors： Sergiev PV,Aleksashin NA,Chugunova AA,Polikanov YS,Dontsova OA

更新日期：2018-02-14 00:00:00

abstract：:Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacter...

journal_title：Nature chemical biology

authors： Li YX,Zhong Z,Hou P,Zhang WP,Qian PY

更新日期：2018-04-01 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

authors： Li J,Jia S,Chen PR

更新日期：2014-12-01 00:00:00

abstract：:Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven...

journal_title：Nature chemical biology

authors： Ly M,Leach FE 3rd,Laremore TN,Toida T,Amster IJ,Linhardt RJ

更新日期：2011-10-09 00:00:00

abstract：:Chemical biology is an interdisciplinary field that is undergoing rapid expansion around the globe. Recently, the Japanese Society for Chemical Biology sponsored its inaugural scientific meeting to discuss research at the interface of chemistry and biology. ...

journal_title：Nature chemical biology

authors： Kikuchi K,Kakeya H

更新日期：2006-08-01 00:00:00

abstract：:Hundreds of cellular proteins require iron cofactors for activity, and cells express systems for their assembly and distribution. Molecular details of the cytosolic iron pool used for iron cofactors are lacking, but iron chaperones of the poly(rC)-binding protein (PCBP) family play a key role in ferrous ion distributi...

journal_title：Nature chemical biology

authors： Patel SJ,Frey AG,Palenchar DJ,Achar S,Bullough KZ,Vashisht A,Wohlschlegel JA,Philpott CC

更新日期：2019-09-01 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

authors： Shestopalov IA,Pitt CL,Chen JK

更新日期：2012-01-29 00:00:00