Bacterial evolution by intelligent design.

abstract：:N-Acetylneuraminic acid lyase (NAL) is a Class I aldolase that catalyzes the reversible condensation of pyruvate with N-acetyl-d-mannosamine (ManNAc) to yield the sialic acid N-acetylneuraminic acid (Neu5Ac). Aldolases are finding increasing use as biocatalysts for the stereospecific synthesis of complex molecules. In...

journal_title：ACS chemical biology

authors： Daniels AD,Campeotto I,van der Kamp MW,Bolt AH,Trinh CH,Phillips SE,Pearson AR,Nelson A,Mulholland AJ,Berry A

更新日期：2014-04-18 00:00:00

abstract：:The indole side chain of tryptophan has latent nucleophilic reactivity at both N1 and all six (nonbridgehead) carbons, which is not generally manifested in post-translational reactions of proteins. On the other hand, all seven positions can be prenylated by the primary metabolite Δ(2)-isopentenyl diphosphate by dimeth...

journal_title：ACS chemical biology

authors： Walsh CT

更新日期：2014-12-19 00:00:00

abstract：:Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 acti...

journal_title：ACS chemical biology

authors： Pollock JA,Larrea MD,Jasper JS,McDonnell DP,McCafferty DG

更新日期：2012-07-20 00:00:00

abstract：:Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive pro...

journal_title：ACS chemical biology

authors： Childs-Disney JL,Disney MD

更新日期：2016-02-19 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：:Numerous cytochrome P450 (CYP) 2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen-π bonds in substrate selectivity and orientation in the active site, structures of four CYP2B6 monoterpenoid complexes were solved by X-ray crystallography. Bornyl bromide exhibited ...

journal_title：ACS chemical biology

authors： Shah MB,Liu J,Zhang Q,Stout CD,Halpert JR

更新日期：2017-05-19 00:00:00

abstract：:Peptidoglycan glycosyltransferases (PGTs), enzymes that catalyze the formation of the glycan chains of the bacterial cell wall, have tremendous potential as antibiotic targets. The moenomycins, a potent family of natural product antibiotics, are the only known active site inhibitors of the PGTs and serve as blueprints...

journal_title：ACS chemical biology

authors： Yuan Y,Fuse S,Ostash B,Sliz P,Kahne D,Walker S

更新日期：2008-07-18 00:00:00

abstract：:Tumor heterogeneity has hampered the development of novel effective therapeutic options for aggressive cancers, including the deadly primary adult brain tumor glioblastoma (GBM). Intratumoral heterogeneity is partially attributed to the tumor initiating cell (TIC) subset that contains highly tumorigenic, stem-like cel...

journal_title：ACS chemical biology

authors： Libby CJ,Zhang S,Benavides GA,Scott SE,Li Y,Redmann M,Tran AN,Otamias A,Darley-Usmar V,Napierala M,Zhang J,Augelli-Szafran CE,Zhang W,Hjelmeland AB

更新日期：2018-08-17 00:00:00

abstract：:Secreted tyrosinase from melanin-forming Streptomyces avermitilis MA4680 was involved in both ortho-hydroxylation and further oxidation of trans-resveratrol, leading to the formation of melanin. This finding was confirmed by constructing deletion mutants of melC(2) and melD(2) encoding extracellular and intracellular ...

journal_title：ACS chemical biology

authors： Lee N,Kim EJ,Kim BG

更新日期：2012-10-19 00:00:00

abstract：:A major risk for patients having estrogen receptor α (ERα)-positive breast cancer is the recurrence of drug-resistant metastases after initial successful treatment with endocrine therapies. Recent studies have implicated a number of activating mutations in the ligand-binding domain of ERα that stabilize the agonist co...

journal_title：ACS chemical biology

authors： Sharma A,Toy W,Guillen VS,Sharma N,Min J,Carlson KE,Mayne CG,Lin S,Sabio M,Greene G,Katzenellenbogen BS,Chandarlapaty S,Katzenellenbogen JA

更新日期：2018-12-21 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：:The LpxC enzyme in the lipid A biosynthetic pathway is one of the most promising and clinically unexploited antibiotic targets for treatment of multidrug-resistant Gram-negative infections. Progress in medicinal chemistry has led to the discovery of potent LpxC inhibitors with a variety of chemical scaffolds and disti...

journal_title：ACS chemical biology

authors： Lee CJ,Liang X,Gopalaswamy R,Najeeb J,Ark ED,Toone EJ,Zhou P

更新日期：2014-01-17 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：:KCNE transmembrane peptides are a family of modulatory beta-subunits that assemble with voltage-gated K+ channels, producing the diversity of potassium currents needed for proper function in a variety of tissues. Although all five KCNE transcripts have been found in cardiac and other tissues, it is unclear whether two...

journal_title：ACS chemical biology

authors： Morin TJ,Kobertz WR

更新日期：2007-07-20 00:00:00

abstract：:To discover chemical probes to further under-stand the function of individual DNA polymerases, we established a generally applicable high-throughput screening. By applying this technique we discovered three novel inhibitor classes of human DNA polymerase λ (DNA Pol λ), a key enzyme to maintain the genetic integrity of...

journal_title：ACS chemical biology

authors： Strittmatter T,Bareth B,Immel TA,Huhn T,Mayer TU,Marx A

更新日期：2011-04-15 00:00:00

abstract：:There is increasing concern that animal and human reproduction may be adversely affected by exposure to xenoestrogens that activate estrogen receptors. There is evidence that one such compound, Bisphenol A (BPA), also induces meiotic and mitotic aneuploidy, suggesting that these kinds of molecules may also have effect...

journal_title：ACS chemical biology

authors： George O,Bryant BK,Chinnasamy R,Corona C,Arterburn JB,Shuster CB

更新日期：2008-03-20 00:00:00

abstract：:Intracellular reactions on nonenzymatic proteins that activate cellular signals are rarely found. We report one example here that a designed peptide derivative undergoes a nucleophilic reaction specifically with a cytosolic PDZ protein inside cells. This reaction led to the activation of ephrin-B reverse signaling, wh...

journal_title：ACS chemical biology

authors： Yu Y,Liu M,Ng TT,Huang F,Nie Y,Wang R,Yao ZP,Li Z,Xia J

更新日期：2016-01-15 00:00:00

abstract：:Endocytosis is a key process in cellular delivery of macromolecules by molecular transporters, although the mechanism of internalization remains unclear. Here, we probe the cellular uptake of streptavidin using biotinylated guanidinoneomycin (biotinGNeo), a low molecular weight guanidinium-rich molecular transporter. ...

journal_title：ACS chemical biology

authors： Inoue M,Tong W,Esko JD,Tor Y

更新日期：2013-07-19 00:00:00

abstract：:Sugar aminotransferases (SATs) are an important class of tailoring enzymes that catalyze the 5'-pyridoxal phosphate (PLP)-dependent stereo- and regiospecific installation of an amino group from an amino acid donor (typically L-Glu or L-Gln) to a corresponding ketosugar nucleotide acceptor. Herein we report the strateg...

journal_title：ACS chemical biology

authors： Wang F,Singh S,Xu W,Helmich KE,Miller MD,Cao H,Bingman CA,Thorson JS,Phillips GN Jr

更新日期：2015-09-18 00:00:00

abstract：:Cutaneous leishmaniasis remains ignored in therapeutic drug discovery programs worldwide. This is mainly because cutaneous leishmaniasis is frequently a disease of impoverished populations in countries where funds are limited for research and patient care. However, the health burden of individuals in endemic areas man...

journal_title：ACS chemical biology

authors： Sharlow ER,Leimgruber S,Murray S,Lira A,Sciotti RJ,Hickman M,Hudson T,Leed S,Caridha D,Barrios AM,Close D,Grögl M,Lazo JS

更新日期：2014-03-21 00:00:00

abstract：:Aldehydes are key intermediates in many cellular processes, from endogenous metabolic pathways like glycolysis to undesired exogenously induced processes such as lipid peroxidation and DNA interstrand cross-linking. Alkyl aldehydes are well documented to be cytotoxic, affecting the functions of DNA and protein, and th...

journal_title：ACS chemical biology

authors： Yuen LH,Saxena NS,Park HS,Weinberg K,Kool ET

更新日期：2016-08-19 00:00:00

abstract：:Phosphatases play key roles in normal physiology and diseases. Studying phosphatases has been both essential and challenging, and the application of conventional genetic and biochemical methods has led to crucial but still limited understanding of their mechanisms, substrates, and exclusive functions within highly int...

journal_title：ACS chemical biology

authors： Fahs S,Lujan P,Köhn M

更新日期：2016-11-18 00:00:00

abstract：:The quest for ever more selective kinase inhibitors as potential future drugs has yielded a large repertoire of chemical probes that are selective for specific kinase conformations. These probes have been useful tools to obtain structural snapshots of kinase conformational plasticity. Similarly, kinetic and thermodyna...

journal_title：ACS chemical biology

authors： Tong M,Seeliger MA

更新日期：2015-01-16 00:00:00

abstract：:Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology. Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conj...

journal_title：ACS chemical biology

authors： Qin K,Zhu Y,Qin W,Gao J,Shao X,Wang YL,Zhou W,Wang C,Chen X

更新日期：2018-08-17 00:00:00

abstract：:HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this context, dendritic cell-specific ICAM-3 grabbing non-inte...

journal_title：ACS chemical biology

authors： Sattin S,Daghetti A,Thépaut M,Berzi A,Sánchez-Navarro M,Tabarani G,Rojo J,Fieschi F,Clerici M,Bernardi A

更新日期：2010-03-19 00:00:00

abstract：:Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are critical to maintain genome integrity, in which the base excision repair pathway plays an essential role. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for removing the deaminated bases f...

journal_title：ACS chemical biology

authors： Zhang Z,Shen J,Yang Y,Li J,Cao W,Xie W

更新日期：2016-06-17 00:00:00

abstract：:Activation by glycosaminoglycans (GAGs) is an emerging trend among extracellular proteases important in disease. ProMMP-7, the zymogen of a matrix metalloproteinase secreted by mucosal epithelial and tumor cells, is activated at their surfaces by sulfated GAGs, but how? ProMMP-7 is activated in trans by representative...

journal_title：ACS chemical biology

authors： Fulcher YG,Sanganna Gari RR,Frey NC,Zhang F,Linhardt RJ,King GM,Van Doren SR

更新日期：2014-04-18 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：:The rational design of environmentally sensitive dyes with superior properties is critical for elucidating the fundamental biological processes and understanding the biophysical behavior of cell membranes. In this study, a novel group of fluorene-based push-pull probes was developed for imaging membrane lipids. The de...

journal_title：ACS chemical biology

authors： Shaya J,Collot M,Bénailly F,Mahmoud N,Mély Y,Michel BY,Klymchenko AS,Burger A

更新日期：2017-12-15 00:00:00

abstract：:Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to sequestration of ...

journal_title：ACS chemical biology

authors： Khan E,Tawani A,Mishra SK,Verma AK,Upadhyay A,Kumar M,Sandhir R,Mishra A,Kumar A

更新日期：2018-01-19 00:00:00