Cholesterol, it's not just for heart disease anymore.

abstract：:Regorafenib (Stivarga) is an oral small molecule kinase inhibitor used to treat metastatic colorectal cancer, hepatocellular carcinomas, and gastrointestinal stromal tumors. Diarrhea is one of the most frequently observed adverse reactions associated with regorafenib. This toxicity may arise from the reactivation of t...

journal_title：ACS chemical biology

authors： Ervin SM,Hanley RP,Lim L,Walton WG,Pearce KH,Bhatt AP,James LI,Redinbo MR

更新日期：2019-12-20 00:00:00

abstract：:The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the f...

journal_title：ACS chemical biology

authors： Wrigley JD,Gavory G,Simpson I,Preston M,Plant H,Bradley J,Goeppert AU,Rozycka E,Davies G,Walsh J,Valentine A,McClelland K,Odrzywol KE,Renshaw J,Boros J,Tart J,Leach L,Nowak T,Ward RA,Harrison T,Andrews DM

更新日期：2017-12-15 00:00:00

abstract：:Photoinduced cross-linking (PIC) has become a powerful tool in chemical biology for the identification and mapping of stable or transient interactions between biomacromolecules and their (unknown) ligands. However, the value of PIC for in vitro and in vivo structural proteomics can be realized only if cross-linking re...

journal_title：ACS chemical biology

authors： Preston GW,Radford SE,Ashcroft AE,Wilson AJ

更新日期：2014-03-21 00:00:00

abstract：:Ammonia lyases catalyze the formation of α,β-unsaturated bonds by the elimination of ammonia from their substrates. This conceptually straightforward reaction has been the emphasis of many studies, with the main focus on the catalytic mechanism of these enzymes and/or the use of these enzymes as catalysts for the synt...

journal_title：ACS chemical biology

authors： de Villiers M,Puthan Veetil V,Raj H,de Villiers J,Poelarends GJ

更新日期：2012-10-19 00:00:00

abstract：:Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-κB signaling in human cells. NSC697923 and BAY 11-7082 both i...

journal_title：ACS chemical biology

authors： Hodge CD,Edwards RA,Markin CJ,McDonald D,Pulvino M,Huen MS,Zhao J,Spyracopoulos L,Hendzel MJ,Glover JN

更新日期：2015-07-17 00:00:00

abstract：:Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes and are emerging as pioneering drug targets. Herein, we present a novel probe, Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling ide...

journal_title：ACS chemical biology

authors： Ward JA,McLellan L,Stockley M,Gibson KR,Whitlock GA,Knights C,Harrigan JA,Jacq X,Tate EW

更新日期：2016-12-16 00:00:00

abstract：:Regulators of G protein signaling (RGS) proteins are key players in regulating signaling via G protein-coupled receptors. RGS proteins directly bind to the Gα-subunits of activated heterotrimeric G-proteins, and accelerate the rate of GTP hydrolysis, thereby rapidly deactivating G-proteins. Using atomistic simulations...

journal_title：ACS chemical biology

authors： Vashisth H,Storaska AJ,Neubig RR,Brooks CL 3rd

更新日期：2013-12-20 00:00:00

abstract：:Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane-associated glycans is more restricted than that of g...

journal_title：ACS chemical biology

authors： Nasir W,Frank M,Kunze A,Bally M,Parra F,Nyholm PG,Höök F,Larson G

更新日期：2017-05-19 00:00:00

abstract：:The neurotoxin saxitoxin and related paralytic shellfish toxins are produced by multiple species of cyanobacteria and dinoflagellates. This study investigates the two saxitoxin-producing strains of Scytonema crispum, CAWBG524 and CAWBG72, isolated in New Zealand. Each strain was previously reported to have a distinct ...

journal_title：ACS chemical biology

authors： Cullen A,D'Agostino PM,Mazmouz R,Pickford R,Wood S,Neilan BA

更新日期：2018-11-16 00:00:00

abstract：:X-ray crystallographic analysis of a bovine antibody (BLV1H12) revealed a unique scaffold in its ultralong heavy chain complementarity determining region 3 (CDR3H) that folds into a solvent exposed, antiparallel β-stranded "stalk" fused with a disulfide cross-linked "knob" domain. This unusual variable region motif pr...

journal_title：ACS chemical biology

authors： Zhang Y,Wang D,Welzel G,Wang Y,Schultz PG,Wang F

更新日期：2013-10-18 00:00:00

abstract：:Generating highly selective probes to interrogate protein kinase function in biological studies remains a challenge, and new strategies are required. Herein, we describe the development of the first highly selective and cell-permeable inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves extensio...

journal_title：ACS chemical biology

authors： Brandvold KR,Steffey ME,Fox CC,Soellner MB

更新日期：2012-08-17 00:00:00

abstract：:The clinical application of siRNA is limited largely by the lack of efficient, cell-specific delivery systems. Antibodies are attractive delivery vehicles for targeted therapy due to their high specificity. In this study we describe the use of a humanized monoclonal antibody (mAb), hu3S193, against Lewis-Y (Le(y)), as...

journal_title：ACS chemical biology

authors： Ma Y,Kowolik CM,Swiderski PM,Kortylewski M,Yu H,Horne DA,Jove R,Caballero OL,Simpson AJ,Lee FT,Pillay V,Scott AM

更新日期：2011-09-16 00:00:00

abstract：:Determining the impact of lipid electrophile-mediated protein damage that occurs during oxidative stress requires a comprehensive analysis of electrophile targets adducted under pathophysiological conditions. Incorporation of ω-alkynyl linoleic acid into the phospholipids of macrophages prior to activation by Kdo2-lip...

journal_title：ACS chemical biology

authors： Beavers WN,Rose KL,Galligan JJ,Mitchener MM,Rouzer CA,Tallman KA,Lamberson CR,Wang X,Hill S,Ivanova PT,Brown HA,Zhang B,Porter NA,Marnett LJ

更新日期：2017-08-18 00:00:00

abstract：:Epigenetic regulation is directed, in part, by the correlated placement of histone post-translational modifications, but the mechanisms controlling correlated modifications are incompletely understood. Correlations arise from crosstalk among modifications and are frequently attributed to protein-protein interactions t...

journal_title：ACS chemical biology

authors： Kornacki JR,Stuparu AD,Mrksich M

更新日期：2015-01-16 00:00:00

abstract：:Fe(III) delivery from blood plasma to cells via the transferrin (Tf) cycle was studied intensively due to its crucial role in Fe homeostasis. Tf-cycle disruptions are linked to anemia, infections, immunodeficiency, and neurodegeneration. Biolayer interferometry (BLI) enabled direct kinetic and thermodynamic measuremen...

journal_title：ACS chemical biology

authors： Levina A,Lay PA

更新日期：2019-05-17 00:00:00

abstract：:The anticancer molecule taxol (Paclitaxel) stands as one of the most medically and economically important natural products. However, despite decades of extensive study, its biosynthesis remains poorly understood. Unpredictable behavior of the first oxygenation enzyme, taxadiene-5α-hydroxylase, which produces a range o...

journal_title：ACS chemical biology

authors： Edgar S,Zhou K,Qiao K,King JR,Simpson JH,Stephanopoulos G

更新日期：2016-02-19 00:00:00

abstract：:Binding of the Fc domain of Immunoglobulin G (IgG) to Fcγ receptors on leukocytes can initiate a series of signaling events resulting in antibody-dependent cell-mediated cytotoxicity (ADCC) and other important immune responses. Fc domains lacking glycosylation at N297 have greatly diminished Fcγ receptor binding and l...

journal_title：ACS chemical biology

authors： Borrok MJ,Jung ST,Kang TH,Monzingo AF,Georgiou G

更新日期：2012-09-21 00:00:00

abstract：:Vitamin A serves essential functions in mammalian biology as a signaling molecule and chromophore. This lipid can be synthesized from more than 50 putative dietary provitamin A precursor molecules which contain at least one unsubstituted β-ionone ring. We here scrutinized the enzymatic properties and substrate specifi...

journal_title：ACS chemical biology

authors： Kelly ME,Ramkumar S,Sun W,Colon Ortiz C,Kiser PD,Golczak M,von Lintig J

更新日期：2018-08-17 00:00:00

abstract：:Phosphoinositides are critical cell-signal mediators present on the plasma membrane. The dynamic change of phosphoinositide concentrations on the membrane including clustering and declustering mediates signal transduction. The importance of phosphoinositides is scored by the fact that they participate in almost all ce...

journal_title：ACS chemical biology

authors： Mondal S,Rakshit A,Pal S,Datta A

更新日期：2016-07-15 00:00:00

abstract：:Several C-β-d-glucopyranosyl azoles have recently been uncovered as among the most potent glycogen phosphorylase (GP) catalytic site inhibitors discovered to date. Toward further exploring their translational potential, ex vivo experiments have been performed for their effectiveness in reduction of glycogenolysis in h...

journal_title：ACS chemical biology

authors： Barr D,Szennyes E,Bokor É,Al-Oanzi ZH,Moffatt C,Kun S,Docsa T,Sipos Á,Davies MP,Mathomes RT,Snape TJ,Agius L,Somsák L,Hayes JM

更新日期：2019-07-19 00:00:00

abstract：:One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAF(V600) mutant melanomas. However, they paradoxically promote th...

journal_title：ACS chemical biology

authors： Molzan M,Kasper S,Röglin L,Skwarczynska M,Sassa T,Inoue T,Breitenbuecher F,Ohkanda J,Kato N,Schuler M,Ottmann C

更新日期：2013-09-20 00:00:00

abstract：:Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene ex...

journal_title：ACS chemical biology

authors： Deochand DK,Meariman JK,Grove A

更新日期：2016-07-15 00:00:00

abstract：:Enzymatic plasticity, as a modern term referring to the functional conversion of an enzyme, is significant for enzymatic activity redesign. The bacterial diterpene cyclase CotB2 is a typical plastic enzyme by which its native form precisely conducts a chemical reaction while its mutants diversify the catalytic functio...

journal_title：ACS chemical biology

authors： Tang X,Zhang F,Zeng T,Li W,Yin S,Wu R

更新日期：2020-10-16 00:00:00

abstract：:Streptolysin S (SLS) is a post-translationally modified peptide cytolysin that is produced by the human pathogen Streptococcus pyogenes. SLS belongs to a large family of azole-containing natural products that are biosynthesized via an evolutionarily conserved pathway. SLS is an important virulence factor during S. pyo...

journal_title：ACS chemical biology

authors： Maxson T,Deane CD,Molloy EM,Cox CL,Markley AL,Lee SW,Mitchell DA

更新日期：2015-05-15 00:00:00

abstract：:Cocaine esterase (CocE) is known as the most efficient natural enzyme for cocaine hydrolysis. The major obstacle to the clinical application of wild-type CocE is the thermoinstability with a half-life of only ∼12 min at 37 °C. The previously designed T172R/G173Q mutant (denoted as enzyme E172-173) with an improved in ...

journal_title：ACS chemical biology

authors： Fang L,Chow KM,Hou S,Xue L,Chen X,Rodgers DW,Zheng F,Zhan CG

更新日期：2014-08-15 00:00:00

abstract：:Ineffective cellular delivery is a common problem in numerous biological applications. Developing delivery reagents that work robustly in a variety of experimental settings remains a challenge. Herein, we report how peptides derived from the prototypical cell penetrating peptide TAT can be used in combination with a s...

journal_title：ACS chemical biology

authors： Allen J,Najjar K,Erazo-Oliveras A,Kondow-McConaghy HM,Brock DJ,Graham K,Hager EC,Marschall ALJ,Dübel S,Juliano RL,Pellois JP

更新日期：2019-12-20 00:00:00

abstract：:Proteins subjected to an electric field and forced to pass through a nanopore induce blockades of ionic current that depend on the protein and nanopore characteristics and interactions between them. Recent advances in the analysis of these blockades have highlighted a variety of phenomena that can be used to study pro...

journal_title：ACS chemical biology

authors： Oukhaled A,Bacri L,Pastoriza-Gallego M,Betton JM,Pelta J

更新日期：2012-12-21 00:00:00

abstract：:The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, ...

journal_title：ACS chemical biology

authors： Chowdhury R,Candela-Lena JI,Chan MC,Greenald DJ,Yeoh KK,Tian YM,McDonough MA,Tumber A,Rose NR,Conejo-Garcia A,Demetriades M,Mathavan S,Kawamura A,Lee MK,van Eeden F,Pugh CW,Ratcliffe PJ,Schofield CJ

更新日期：2013-07-19 00:00:00

abstract：:Engineering gene circuits with novel functions holds promise for broad applications in biology, engineering, and medicine. Directed evolution complements rational design as an important strategy for optimizing gene circuits and circuit elements. ...

journal_title：ACS chemical biology

authors： Song H,You L

更新日期：2006-12-20 00:00:00

abstract：:The Morita-Baylis-Hillman reaction forms a carbon-carbon bond between the α-carbon of a conjugated carbonyl compound and a carbon electrophile. The reaction mechanism involves Michael addition of a nucleophile catalyst at the carbonyl β-carbon, followed by bond formation with the electrophile and catalyst disassociati...

journal_title：ACS chemical biology

authors： Bjelic S,Nivón LG,Çelebi-Ölçüm N,Kiss G,Rosewall CF,Lovick HM,Ingalls EL,Gallaher JL,Seetharaman J,Lew S,Montelione GT,Hunt JF,Michael FE,Houk KN,Baker D

更新日期：2013-04-19 00:00:00