Development of a covalent inhibitor of gut bacterial bile salt hydrolases.

abstract：: ...

journal_title：Nature chemical biology

authors： Song Y

更新日期：2019-01-01 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

authors： Gloster TM,Zandberg WF,Heinonen JE,Shen DL,Deng L,Vocadlo DJ

更新日期：2011-03-01 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

authors： Hsu KL,Tsuboi K,Adibekian A,Pugh H,Masuda K,Cravatt BF

更新日期：2012-12-01 00:00:00

abstract：:The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of plant growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-b...

journal_title：Nature chemical biology

authors： Uchida N,Takahashi K,Iwasaki R,Yamada R,Yoshimura M,Endo TA,Kimura S,Zhang H,Nomoto M,Tada Y,Kinoshita T,Itami K,Hagihara S,Torii KU

更新日期：2018-03-01 00:00:00

abstract：:Post-transcriptional RNA modifications can be dynamic and might have functions beyond fine-tuning the structure and function of RNA. Understanding these RNA modification pathways and their functions may allow researchers to identify new layers of gene regulation at the RNA level. ...

journal_title：Nature chemical biology

authors： He C

更新日期：2010-12-01 00:00:00

abstract：:We engineered a photoactivatable system for rapidly and reversibly exporting proteins from the nucleus by embedding a nuclear export signal in the LOV2 domain from phototropin 1. Fusing the chromatin modifier Bre1 to the photoswitch, we achieved light-dependent control of histone H2B monoubiquitylation in yeast, revea...

journal_title：Nature chemical biology

authors： Yumerefendi H,Lerner AM,Zimmerman SP,Hahn K,Bear JE,Strahl BD,Kuhlman B

更新日期：2016-06-01 00:00:00

abstract：:Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioac...

journal_title：Nature chemical biology

authors： Meesters C,Mönig T,Oeljeklaus J,Krahn D,Westfall CS,Hause B,Jez JM,Kaiser M,Kombrink E

更新日期：2014-10-01 00:00:00

abstract：:Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...

journal_title：Nature chemical biology

authors： Olson CM,Jiang B,Erb MA,Liang Y,Doctor ZM,Zhang Z,Zhang T,Kwiatkowski N,Boukhali M,Green JL,Haas W,Nomanbhoy T,Fischer ES,Young RA,Bradner JE,Winter GE,Gray NS

更新日期：2018-02-01 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：: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

authors： Italia JS,Addy PS,Wrobel CJ,Crawford LA,Lajoie MJ,Zheng Y,Chatterjee A

更新日期：2017-04-01 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

authors： Liu KI,Ramli MN,Woo CW,Wang Y,Zhao T,Zhang X,Yim GR,Chong BY,Gowher A,Chua MZ,Jung J,Lee JH,Tan MH

更新日期：2016-11-01 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：:The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshapi...

journal_title：Nature chemical biology

authors： Fang C,Philips SJ,Wu X,Chen K,Shi J,Shen L,Xu J,Feng Y,O'Halloran TV,Zhang Y

更新日期：2021-01-01 00:00:00

abstract：:Nature is a diverse and rich source of bioactive pathways or novel building blocks for synthetic biology. In this Perspective, we describe the emerging research field in which metagenomes are functionally interrogated using synthetic biology. This approach substantially expands the set of identified biological activit...

journal_title：Nature chemical biology

authors： van der Helm E,Genee HJ,Sommer MOA

更新日期：2018-08-01 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

authors： Hong H,Szabo G,Tamm LK

更新日期：2006-11-01 00:00:00

abstract：:Learning regulatory networks from genomics data is an important problem with applications spanning all of biology and biomedicine. Functional genomics projects offer a cost-effective means of greatly expanding the completeness of our regulatory models, and for some prokaryotic organisms they offer a means of learning ...

journal_title：Nature chemical biology

authors： Bonneau R

更新日期：2008-11-01 00:00:00

abstract：:Bacteria are thought to cope with fluctuating environmental solute concentrations primarily by adjusting the osmolality of their cytoplasm. To obtain insights into the underlying metabolic adaptations, we analyzed the global metabolic response of Escherichia coli to sustained hyperosmotic stress using nontargeted mass...

journal_title：Nature chemical biology

authors： Sévin DC,Sauer U

更新日期：2014-04-01 00:00:00

abstract：:To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...

journal_title：Nature chemical biology

authors： Zhao EM,Suek N,Wilson MZ,Dine E,Pannucci NL,Gitai Z,Avalos JL,Toettcher JE

更新日期：2019-06-01 00:00:00

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

authors： Burton RA,Gidley MJ,Fincher GB

更新日期：2010-10-01 00:00:00

abstract：:Binding to the primary receptor, CD4, triggers conformational changes in the metastable HIV-1 envelope glycoprotein (Env) trimer ((gp120-gp41)3) that are important for virus entry into host cells. These changes include an 'opening' of the trimer, creation of a binding site for the CCR5 co-receptor and formation and/or...

journal_title：Nature chemical biology

authors： Herschhorn A,Gu C,Espy N,Richard J,Finzi A,Sodroski JG

更新日期：2014-10-01 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

authors： Baldwin AJ,Kay LE

更新日期：2009-11-01 00:00:00

abstract：:Single-molecule observations reveal that lipid- and protein-based interactions jointly contribute to the interactions among glycosylphosphatidylinositol-anchored proteins in membranes. Understanding these interactions will help to refine long-evolving (and still debated) models of 'raft' domains in biological membrane...

journal_title：Nature chemical biology

authors： Silvius JR

更新日期：2012-09-01 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：: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：:Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (...

journal_title：Nature chemical biology

authors： Wagner TE,Becraft JR,Bodner K,Teague B,Zhang X,Woo A,Porter E,Alburquerque B,Dobosh B,Andries O,Sanders NN,Beal J,Densmore D,Kitada T,Weiss R

更新日期：2018-11-01 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

authors： Mishanina TV,Libiad M,Banerjee R

更新日期：2015-07-01 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

authors： Carnes EC,Lopez DM,Donegan NP,Cheung A,Gresham H,Timmins GS,Brinker CJ

更新日期：2010-01-01 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

authors： Gouzy A,Larrouy-Maumus G,Wu TD,Peixoto A,Levillain F,Lugo-Villarino G,Guerquin-Kern JL,de Carvalho LP,Poquet Y,Neyrolles O

更新日期：2013-11-01 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

authors： Jia G,Fu Y,Zhao X,Dai Q,Zheng G,Yang Y,Yi C,Lindahl T,Pan T,Yang YG,He C

更新日期：2011-10-16 00:00:00

abstract：:N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (...

journal_title：Nature chemical biology

authors： Liu TW,Myschyshyn M,Sinclair DA,Cecioni S,Beja K,Honda BM,Morin RD,Vocadlo DJ

更新日期：2017-02-01 00:00:00