Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation.

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：:Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore 11-cis-retinal and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the ...

journal_title：Nature chemical biology

authors： Maeda A,Golczak M,Chen Y,Okano K,Kohno H,Shiose S,Ishikawa K,Harte W,Palczewska G,Maeda T,Palczewski K

更新日期：2011-12-25 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

authors： Tarrant MK,Rho HS,Xie Z,Jiang YL,Gross C,Culhane JC,Yan G,Qian J,Ichikawa Y,Matsuoka T,Zachara N,Etzkorn FA,Hart GW,Jeong JS,Blackshaw S,Zhu H,Cole PA

更新日期：2012-01-22 00:00:00

abstract：:The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, bu...

journal_title：Nature chemical biology

authors： Smith AT,Barupala D,Stemmler TL,Rosenzweig AC

更新日期：2015-09-01 00:00:00

abstract：:Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria ...

journal_title：Nature chemical biology

authors： Adhikari AA,Seegar TCM,Ficarro SB,McCurry MD,Ramachandran D,Yao L,Chaudhari SN,Ndousse-Fetter S,Banks AS,Marto JA,Blacklow SC,Devlin AS

更新日期：2020-03-01 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：:5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA ...

journal_title：Nature chemical biology

authors： Bachman M,Uribe-Lewis S,Yang X,Burgess HE,Iurlaro M,Reik W,Murrell A,Balasubramanian S

更新日期：2015-08-01 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

authors： Falsey RR,Marron MT,Gunaherath GM,Shirahatti N,Mahadevan D,Gunatilaka AA,Whitesell L

更新日期：2006-01-01 00:00:00

abstract：:Long noncoding RNAs (lncRNAs) are important for gene expression, but little is known about their structures. RepA is a 1.6-kb mouse lncRNA comprising the same sequence as the 5' region of Xist, including A and F repeats. It has been proposed to facilitate the initiation and spread of X-chromosome inactivation, althoug...

journal_title：Nature chemical biology

authors： Liu F,Somarowthu S,Pyle AM

更新日期：2017-03-01 00:00:00

abstract：:Occurrence of the BCR-ABL(T315I) gatekeeper mutation is among the most pressing challenges in the therapy of chronic myeloid leukemia (CML). Several BCR-ABL inhibitors have multiple targets and pleiotropic effects that could be exploited for their synergistic potential. Testing combinations of such kinase inhibitors i...

journal_title：Nature chemical biology

authors： Winter GE,Rix U,Carlson SM,Gleixner KV,Grebien F,Gridling M,Müller AC,Breitwieser FP,Bilban M,Colinge J,Valent P,Bennett KL,White FM,Superti-Furga G

更新日期：2012-11-01 00:00:00

abstract：:This Commentary clarifies the meaning of the funnel diagram, which has been widely cited in papers on protein folding. To aid in the analysis of the funnel diagram, this Commentary reviews historical approaches to understanding the mechanism of protein folding. The primary role of free energy in protein folding is dis...

journal_title：Nature chemical biology

authors： Karplus M

更新日期：2011-06-17 00:00:00

abstract：:Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABAA (γ-aminobutyric acid type A) receptors, but where it binds to this receptor is not known and has been a matter of some debate. We synthesized a new propofol analog photolabeling reagent whose biological...

journal_title：Nature chemical biology

authors： Yip GM,Chen ZW,Edge CJ,Smith EH,Dickinson R,Hohenester E,Townsend RR,Fuchs K,Sieghart W,Evers AS,Franks NP

更新日期：2013-11-01 00:00:00

abstract：:Designing selective inhibitors of proteases has proven problematic, in part because pharmacophores that confer potency exploit the conserved catalytic apparatus. We developed a fundamentally different approach by designing irreversible inhibitors that target noncatalytic cysteines that are structurally unique to a tar...

journal_title：Nature chemical biology

authors： Hagel M,Niu D,St Martin T,Sheets MP,Qiao L,Bernard H,Karp RM,Zhu Z,Labenski MT,Chaturvedi P,Nacht M,Westlin WF,Petter RC,Singh J

更新日期：2011-01-01 00:00:00

abstract：:A 2.4-Å-resolution X-ray crystal structure of the carrier-protein-independent halogenase WelO5 in complex with its welwitindolinone precursor substrate, 12-epi-fischerindole U, reveals that the C13 chlorination target is proximal to the anticipated site of the oxo group in a presumptive cis-halo-oxo-iron(IV) (haloferr...

journal_title：Nature chemical biology

authors： Mitchell AJ,Zhu Q,Maggiolo AO,Ananth NR,Hillwig ML,Liu X,Boal AK

更新日期：2016-08-01 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

authors： Rigo F,Hua Y,Chun SJ,Prakash TP,Krainer AR,Bennett CF

更新日期：2012-04-15 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：:Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened seven parasite lines for differences in responses to 1,279 bioactive chemicals. Hundreds of compounds were active in i...

journal_title：Nature chemical biology

authors： Yuan J,Johnson RL,Huang R,Wichterman J,Jiang H,Hayton K,Fidock DA,Wellems TE,Inglese J,Austin CP,Su XZ

更新日期：2009-10-01 00:00:00

abstract：:The catalytic versatility of cytochrome P450 monooxygenases is remarkable. Here, we present mechanistic and structural characterizations of TleB from Streptomyces blastmyceticus and its homolog HinD from Streptoalloteichus hindustanus, which catalyze unusual intramolecular C-N bond formation to generate indolactam V f...

journal_title：Nature chemical biology

authors： He F,Mori T,Morita I,Nakamura H,Alblova M,Hoshino S,Awakawa T,Abe I

更新日期：2019-12-01 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：:Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed ma...

journal_title：Nature chemical biology

authors： Liu SL,Sheng R,Jung JH,Wang L,Stec E,O'Connor MJ,Song S,Bikkavilli RK,Winn RA,Lee D,Baek K,Ueda K,Levitan I,Kim KP,Cho W

更新日期：2017-03-01 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：: ...

journal_title：Nature chemical biology

authors： Song Y

更新日期：2019-01-01 00:00:00

abstract：:ADP-ribosylation is a post-translational modification that is known to be involved in cellular homeostasis and stress but has been challenging to analyze biochemically. To facilitate the detection of ADP-ribosylated proteins, we show that an alkyne-adenosine analog, N6-propargyl adenosine (N6pA), is metabolically inco...

journal_title：Nature chemical biology

authors： Westcott NP,Fernandez JP,Molina H,Hang HC

更新日期：2017-03-01 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：:The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks o...

journal_title：Nature chemical biology

authors： Chen J,Sutter BM,Shi L,Tu BP

更新日期：2017-11-01 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：: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

authors： Palmer CM,Guerinot ML

更新日期：2009-05-01 00:00:00

abstract：:Despite the fundamental roles of sialyl- and fucosyltransferases in mammalian physiology, there are few pharmacological tools to manipulate their function in a cellular setting. Although fluorinated analogs of the donor substrates are well-established transition state inhibitors of these enzymes, they are not membrane...

journal_title：Nature chemical biology

authors： Rillahan CD,Antonopoulos A,Lefort CT,Sonon R,Azadi P,Ley K,Dell A,Haslam SM,Paulson JC

更新日期：2012-07-01 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

authors： Kathayat RS,Elvira PD,Dickinson BC

更新日期：2017-02-01 00:00:00

abstract：:Intrinsically disordered regions (IDRs) of proteins often regulate function upon post-translational modification (PTM) through interactions with folded domains. An IDR linking two α-helices (α1-α2) of the antiapoptotic protein Bcl-xL experiences several PTMs that reduce antiapoptotic activity. Here, we report that PTM...

journal_title：Nature chemical biology

authors： Follis AV,Llambi F,Kalkavan H,Yao Y,Phillips AH,Park CG,Marassi FM,Green DR,Kriwacki RW

更新日期：2018-05-01 00:00:00