Abstract:
:Dicamba monooxygenase (DMO) catalyzes the O-demethylation of dicamba (3,6-dichloro-2-methoxybenzoate) to produce 3,6-dichlorosalicylate and formaldehyde. Recent crystallographic studies suggest that DMO catalyzes the challenging oxidation of a saturated C-H bond within the methyl group of dicamba to form a hemiacetal intermediate. Testing of this hypothesis was made possible by our development of two new independent techniques. As a novel method to allow use of (18)O2 to follow reaction products, bisulfite was used to trap newly formed (18)O-formaldehyde in the stable adduct, hydroxymethanesulfonate (HMS(-)), and thereby prevent the rapid exchange of (18)O in formaldehyde with (16)O in water. The second technique utilized unique properties of Pseudomonas putida formaldehyde dehydrogenase that allow rapid conversion of (18)O-formaldehyde into stable and easily detectable (18)O-formic acid. Experiments using these two new techniques provided compelling evidence for DMO-catalyzed oxidation of the methyl group of dicamba, thus validating a mechanism for DMO [and for vanillate monooxygenase, a related Rieske nonheme iron monooxygenase] that involves the difficult oxidation of a saturated C-H bond.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Jiang W,Wilson MA,Weeks DPdoi
10.1021/cb400154asubject
Has Abstractpub_date
2013-08-16 00:00:00pages
1687-91issue
8eissn
1554-8929issn
1554-8937journal_volume
8pub_type
杂志文章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::The plant hormone auxin is a master regulator of plant growth and development. By regulating rates of cell division and elongation and triggering specific patterning events, indole 3-acetic acid (IAA) regulates almost every aspect of plant development. The perception of auxin involves the formation of a ternary comple...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200404c
更新日期:2012-03-16 00:00:00
abstract::Invertebrate animal models (mainly the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster) are gaining momentum as screening tools in drug discovery. These organisms combine genetic amenability, low cost, and culture conditions compatible with large-scale screens. Their main advantage is to allo...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb700009m
更新日期:2007-04-24 00:00:00
abstract::Angiogenesis, the formation of new blood vessels, is implicated in a number of important human diseases, including cancer, diabetic retinopathy, and rheumatoid arthritis. To identify clinically useful angiogenesis inhibitors, we assembled and screened a library of mostly Food and Drug Administration-approved drugs for...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb600362d
更新日期:2007-04-24 00:00:00
abstract::Methods for the rapid identification of defined cell growth conditions are lacking. This deficiency is a major barrier to the investigation and application of human embryonic stem (ES) cells. To address this problem, we developed a method for generating arrays of self-assembled monolayers (SAMs) in which each element ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb700032u
更新日期:2007-05-22 00:00:00
abstract::This report highlights the advantages of low-affinity, multivalent interactions to recognize one cell type over another. Our goal was to devise a strategy to mediate selective killing of tumor cells, which are often distinguished from normal cells by their higher levels of particular cell surface receptors. To test wh...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb6003788
更新日期:2007-02-20 00:00:00
abstract::Cell-permeable small molecules can be used to modulate protein function selectively, rapidly, reversibly, and conditionally with temporal and quantitative control in biological systems. The identification of these chemical probes can require the screening of large numbers of small molecules. With the advent of new tec...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb600321j
更新日期:2007-01-23 00:00:00
abstract::Understanding the complex biochemical mechanisms that underlie the regulation, toxicity, and protein binding of metal ions requires the ability to analyze the metal content of individual proteins in complex mixtures. In this issue of ACS Chemical Biology, a technique combining gel electrophoresis with synchrotron X-ra...
journal_title:ACS chemical biology
pub_type: 评论,杂志文章
doi:10.1021/cb100145z
更新日期:2010-06-18 00:00:00
abstract::Modern visualization techniques are affording a peek into complex cellular processes. A recent paper describes an automated fluorescence microscopy method to map the subcellular localization of up to 100 different proteins in the same sample. ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb600461v
更新日期:2006-12-15 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::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::Botulinum neurotoxins (BoNTs) are the most potent toxins known to man and a significant threat as weapons of bioterrorism. BoNTs contain a metalloprotease domain that blocks neurotransmitter release in nerve terminals, resulting in a descending, flaccid paralysis with a 5-10% mortality rate. Existing treatment options...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00937
更新日期:2019-01-18 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
pub_type: 杂志文章
doi:10.1021/cb100382m
更新日期:2011-04-15 00:00:00
abstract::Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. Here we report that the cell wall of S. aureus can be covalently re-engineered to contain non-native small molecules. This process makes use of endogenous levels of the bacterial enzyme sortase A (...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb100195d
更新日期:2010-12-17 00:00:00
abstract::Benzodiazepines are clinically relevant drugs that bind to GABAA neurotransmitter receptors at the α+/γ2- interfaces and thereby enhance GABA-induced chloride ion flux leading to neuronal hyperpolarization. However, the structural basis of benzodiazepine interactions with their high-affinity site at GABAA receptors is...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00144
更新日期:2018-08-17 00:00:00
abstract::We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE p...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb500388m
更新日期:2014-11-21 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
pub_type: 信件
doi:10.1021/cb700089s
更新日期:2007-07-20 00:00:00
abstract::Next-generation DNA sequencing technologies have led to a massive accumulation of genomic and transcriptomic data from patients and healthy individuals. The major challenge ahead is to understand the functional significance of the elements of the human genome and transcriptome, and implications for diagnosis and treat...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/acschembio.7b00657
更新日期:2018-02-16 00:00:00
abstract::BRD4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding sites and competitively inhibit BET protein interaction with acetylated chromatin...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00058
更新日期:2020-04-17 00:00:00
abstract::The β-hydroxylation of l-histidine is the first step in the biosynthesis of the imidazolone base of the antifungal drug nikkomycin. The cytochrome P450 (NikQ) hydroxylates the amino acid while it is appended via a phosphopantetheine linker to the non-ribosomal peptide synthetase (NRPS) NikP1. The latter enzyme is comp...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00081
更新日期:2017-05-19 00:00:00
abstract::A biophysical understanding of the mechanistic, chemical, and physical origins underlying antibiotic action and resistance is vital to the discovery of novel therapeutics and the development of strategies to combat the growing emergence of antibiotic resistance. The site-specific introduction of stable-isotope labels ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b01054
更新日期:2020-05-15 00:00:00
abstract::The past several years have seen numerous reports of new chemical modifications for use in RNA. In addition, in that time period, we have seen the discovery of several previously unknown naturally occurring modifications that impart novel properties on the parent RNAs. In this review, we describe recent discoveries in...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb200422t
更新日期:2012-01-20 00:00:00
abstract::Insights into the thermodynamic and kinetic signature of the transient opening of a protein-binding pocket resulting from accommodation of suitable substituents attached to a given parent ligand scaffold are presented. As a target, we selected human aldose reductase, an enzyme involved in the development of late-stage...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00062
更新日期:2017-05-19 00:00:00
abstract::It has been known for nearly a half century that human tumors, including those derived from the nervous system such as glioblastomas, medulloblastoma, and neuroblastomas are much more sensitive than normal tissues to l-methionine (l-Met) starvation. More recently, systemic l-Met depletion by administration of Pseudomo...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300335j
更新日期:2012-11-16 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
pub_type: 杂志文章
doi:10.1021/cb3006227
更新日期:2013-04-19 00:00:00
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
pub_type: 杂志文章
doi:10.1021/cb500067z
更新日期:2014-04-18 00:00:00
abstract::The nonheme diiron enzyme cyanobacterial aldehyde deformylating oxygenase, cADO, catalyzes the highly unusual deformylation of aliphatic aldehydes to alkanes and formate. We have determined crystal structures for the enzyme with a long-chain water-soluble aldehyde and medium-chain carboxylic acid bound to the active s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb500343j
更新日期:2014-11-21 00:00:00
abstract::The steady increase in the prevalence of multidrug-resistant Staphylococcus aureus has made the search for novel antibiotics to combat this clinically important pathogen an urgent matter. In an effort to discover antibacterials with new chemical structures and mechanisms, we performed a growth inhibition screen of a s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00982
更新日期:2020-07-17 00:00:00
abstract::Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00170
更新日期:2017-06-16 00:00:00
abstract::Whereas the C. elegans genome was sequenced many years ago, the role of small molecule signals in its biology is still poorly understood. A recent publication reports the identification of two steroidal signaling molecules that regulate C. elegans reproductive development and dauer diapause via the nuclear receptor DA...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb600173t
更新日期:2006-05-23 00:00:00