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_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Song H,You Ldoi
10.1021/cb6004596subject
Has Abstractpub_date
2006-12-20 00:00:00pages
681-2issue
11eissn
1554-8929issn
1554-8937journal_volume
1pub_type
评论,杂志文章,评审abstract::APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200440y
更新日期:2012-03-16 00:00:00
abstract::Terpenes are ubiquitous natural chemicals with diverse biological functions spanning all three domains of life. In specialized metabolism, the active sites of terpene synthases (TPSs) evolve in shape and reactivity to direct the biosynthesis of a myriad of chemotypes for organismal fitness. As most terpene biosynthesi...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b00539
更新日期:2015-11-20 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
pub_type: 杂志文章
doi:10.1021/cb4003464
更新日期:2013-09-20 00:00:00
abstract::The development of HIV-1 protease inhibitors has been the historic paradigm of rational structure-based drug design, where structural and thermodynamic analyses have assisted in the discovery of novel inhibitors. While the total enthalpy and entropy change upon binding determine the affinity, often the thermodynamics ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300191k
更新日期:2012-09-21 00:00:00
abstract::Small molecules are widely used in chemical biology without complete knowledge of their target profile, at risk of deriving conclusions that ignore potential confounding effects from unknown off-target interactions. The prediction and further experimental confirmation of novel affinities for PJ34 on Pim1 (IC(50) = 3.7...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300317y
更新日期:2012-12-21 00:00:00
abstract::Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (1), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthe...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00564
更新日期:2020-09-18 00:00:00
abstract::Leishmaniases affect the poorest people on earth and have no effective drug therapy. Here, we present the crystal structure of the mitochondrial isoform of class I fumarate hydratase (FH) from Leishmania major and compare it to the previously determined cytosolic Leishmania major isoform. We further describe the mecha...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00972
更新日期:2019-02-15 00:00:00
abstract::Diversity of scaffold structure and function is a hallmark of the >50,000 isoprenoid natural products such as taxol. Whereas most members of this class are assembled by iterative head-to-tail enzymatic joining reactions between delta2- and delta3-isopentenyl diphosphate (IPP) monomers, dimerization of two delta2-IPP m...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb700094s
更新日期:2007-05-22 00:00:00
abstract::Terpene synthases (TS) are classified into two broad types, Class I and II, based on the chemical strategy for initial carbocation formation and motif sequences of the catalytic site. We have recently identified a new class of enzymes, Class IB, showing the acceptability of long (C20-C35) prenyl-diphosphates as substr...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00145
更新日期:2020-06-19 00:00:00
abstract::Hydrogen sulfide (H2S) is an important gasotransmitter and biomolecule, and many synthetic small-molecule H2S donors have been developed for H2S-related research. One important class of triggerable H2S donors is self-immolative thiocarbamates, which function by releasing carbonyl sulfide (COS), which is rapidly conver...
journal_title:ACS chemical biology
pub_type: 信件
doi:10.1021/acschembio.8b00981
更新日期:2019-02-15 00:00:00
abstract::Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b01070
更新日期:2016-05-20 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
pub_type: 杂志文章
doi:10.1021/acschembio.8b01100
更新日期:2019-05-17 00:00:00
abstract::Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of elect...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00031
更新日期:2020-06-19 00:00:00
abstract::Novel strategies are needed to modulate β-cell differentiation and function as potential β-cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on β-cells...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b00993
更新日期:2016-04-15 00:00:00
abstract::The innate immune system provides the first line of defense against pathogens through the recognition of nonspecific patterns in RNA to protect the cell in a generalized way. The human RNA-activated protein kinase, PKR, is a dsRNA binding protein and an essential sensor in the innate immune response, which recognizes ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00081
更新日期:2016-04-15 00:00:00
abstract::FAT10 is a ubiquitin-like protein suggested to target proteins for proteasomal degradation. It is highly upregulated upon pro-inflammatory cytokines, namely, TNFα, IFNγ, and IL6, and was found to be highly expressed in various epithelial cancers. Evidence suggests that FAT10 is involved in cancer development and may h...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00667
更新日期:2019-12-20 00:00:00
abstract::The heterologous biosynthesis of complex natural products has enabled access to polyketide, nonribosomal peptide, isoprenoid, and other compounds with wide-spanning societal value. Though several surrogate host systems exist, Escherichia coli is often a preferred choice due to its rapid growth kinetics and extensive m...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00827
更新日期:2020-05-15 00:00:00
abstract::The ever-growing drug resistance problem worldwide highlights the urgency to discover and develop new drugs. Microbial natural products are a prolific source of drugs. Genome sequencing has revealed a tremendous amount of uncharacterized natural product biosynthetic gene clusters (BGCs) encoded within microbial genome...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00581
更新日期:2020-09-18 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
pub_type: 杂志文章,评审
doi:10.1021/acschembio.6b00570
更新日期:2016-11-18 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
pub_type: 杂志文章
doi:10.1021/cb400898t
更新日期:2014-04-18 00:00:00
abstract::Regulation of gene expression by RNA processing mechanisms is now understood to be an important level of control in mammalian cells. Regulation at the level of RNA transcription, splicing, polyadenylation, nucleo-cytoplasmic transport, and translation into polypeptides has been well-studied. Alternative RNA processing...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb800138w
更新日期:2008-10-17 00:00:00
abstract::Plasmodium falciparum thymidylate synthase-dihydrofolate reductase (TS-DHFR) is an essential enzyme in folate biosynthesis and a major malarial drug target. This bifunctional enzyme thus presents different design approaches for developing novel inhibitors against drug-resistant mutants. We performed a high-throughput ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb8002804
更新日期:2009-01-16 00:00:00
abstract::Platinum-based drugs have been used to successfully treat diverse cancers for several decades. Cisplatin, the original compound of this class, cross-links DNA, resulting in cell cycle arrest and cell death via apoptosis. Cisplatin is effective against several tumor types, yet it exhibits toxic side effects and tumors ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300320d
更新日期:2012-11-16 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
pub_type: 杂志文章
doi:10.1021/cb5004527
更新日期:2015-01-16 00:00:00
abstract::The publication of the first high-resolution crystal structure of a eukaryotic Cys-loop receptor, GluClα, has provided valuable structural information on this important class of ligand-gated ion channels (LGIC). However, limited functional data exist for the GluCl receptors. Before applying the structural insights fro...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb500323d
更新日期:2014-10-17 00:00:00
abstract::RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb4001553
更新日期:2013-07-19 00:00:00
abstract::Antivirulence strategies addressing bacterial pathogenicity without exhibiting growth inhibition effects represent a novel approach to overcome today's crisis in antibiotic development. In recent studies, we examined various inhibitors of PqsD, an enzyme involved in formation of Pseudomonas aeruginosa cell-to-cell sig...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb400530d
更新日期:2013-12-20 00:00:00
abstract::Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis of secondary metabolite gene expression...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00240
更新日期:2019-06-21 00:00:00
abstract::N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer's disease. One approach to enhance the function of NMDAR is...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00913
更新日期:2017-02-17 00:00:00
abstract::Mutations in the NPHP1 gene, coding for human nephrocystin-1 (NPHP1), cause the autosomal recessive disease nephronophthisis, the most common cause of end-stage renal disease in children and adolescents. The function and structure of NPHP1 are still poorly characterized. NPHP1 presents a modular structure well in keep...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00582
更新日期:2019-08-16 00:00:00