Abstract:
:Nuclease footprinting techniques have been employed to investigate the interaction between the diuretic drug amiloride, a sodium channel blocker with potential therapeutic use in the treatment of cystic fibrosis, and three DNA fragments of defined sequence. Using either DNAse I or micrococcal nuclease as probes, an unusual pattern of sequence-selective recognition of DNA has been detected. Amiloride binds selectively to sites rich in adenine and thymine residues, frequently with an apparent preference for 5'-TpX-3' steps, and discriminates strongly against GC-rich sequences which are sometimes cut more readily in the presence of the drug compared to the control. A detailed comparison with the actions of known selective DNA-binding antibiotics and drugs reveals a unique pattern of binding sites, different from those of typical intercalators on the one hand and those of minor groove-binders on the other. Amiloride is believed to adopt a pH-dependent tricyclic hydrogen-bonded conformation in solution which allows it to intercalate into DNA; consistent with this belief, we find that the footprinting pattern largely disappears at pH values above the pKa. Preliminary studies with three amiloride analogues have indicated the importance of two functional groups in the recognition of DNA. The possible relevance of selective DNA binding to activity in vivo is considered.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Bailly C,Cuthbert AW,Gentle D,Knowles MR,Waring MJdoi
10.1021/bi00061a008subject
Has Abstractpub_date
1993-03-16 00:00:00pages
2514-24issue
10eissn
0006-2960issn
1520-4995journal_volume
32pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::New isoforms of CYP51 (sterol 14alpha-demethylase), an essential enzyme in sterol biosynthesis and primary target of azole antimycotic drugs, are found in pathogenic protists, Trypanosoma brucei(TB), T. vivax, T. cruzi, and Leishmania major. The sequences share approximately 80% amino acid identity and are approximate...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048967t
更新日期:2004-08-24 00:00:00
abstract::To better understand origin recognition and initiation of DNA replication, we have examined by NMR complexes formed between the origin-binding domain of SV40 T antigen (T-ag-obd), the initiator protein of the SV40 virus, and cognate and noncognate DNA oligomers. The results reveal two structural effects associated wit...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi030228+
更新日期:2004-06-08 00:00:00
abstract::It is known that, while melittin at micromolar concentrations is unfolded under conditions of low ionic strength at neutral pH, it adopts a tetrameric alpha-helical structure under conditions of high ionic strength, at alkaline pH, or at high peptide concentrations. To understand the mechanism of the conformational tr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00118a014
更新日期:1992-01-28 00:00:00
abstract::Rabbit lung flavin-containing monooxygenase (FMO, EC 1.14.13.8) was denatured, reduced, carboxymethylated, digested with endoproteinase Glu-C or trypsin, and subjected to mass spectrometric analysis. The amino acid sequences of selected peptides were determined by tandem mass spectrometry. Over 90% of rabbit lung FMO ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00105a012
更新日期:1991-10-15 00:00:00
abstract::The bovine adrenodoxin gene gives rise to two species of mRNA differing only at their 5'-ends. The synthesis of these two types of mRNA in bovine adrenal cortical cells is regulated transcriptionally in part by ACTH via the action of cAMP. Examination of the 5'-end of the adrenodoxin gene revealed that each mRNA conta...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00123a027
更新日期:1992-03-03 00:00:00
abstract::For many different enveloped viruses the crystal structure of the fusion protein core has been established. A striking conservation in the tertiary and quaternary arrangement of these core structures is repeatedly revealed among members of diverse families. It has been proposed that the primary role of the core involv...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0255322
更新日期:2002-04-09 00:00:00
abstract::By use of six highly purified exoglycosidases with well-defined specificity, the oligosaccharide units of human plasma beta 2-glycoprotein I (beta 2I) were modified by sequential enzymatic degradation. The released monosaccharides (NeuAc, Gal, GlcNAc, and Man) were quantified, and the carbohydrate compositions of the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00478a020
更新日期:1990-07-03 00:00:00
abstract::Multielectron multiproton reactions play an important role in both biological systems and chemical reactions involved in energy storage and manipulation. A key strategy employed by nature in achieving such complex chemistry is the use of proton-coupled redox steps. Cytochrome c nitrite reductase (ccNiR) catalyzes the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi500854p
更新日期:2014-09-09 00:00:00
abstract::The PufX membrane protein is essential for photosynthetic growth of Rhodobacter sphaeroides because it is required for multiple-turnover electron transfer under anaerobic conditions [see accompanying article; Barz, W. P., Francia, F., Venturoli, G., Melandri, B. A., Verméglio, A., & Oesterhelt, D. (1995) Biochemistry ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00046a033
更新日期:1995-11-21 00:00:00
abstract::Phthalate dioxygenase from Pseudomonas cepacia contains a mononuclear ferrous center that is strictly required for catalytic oxygen activation. The spectroscopic characterization of this iron site and its ligand interactions has been complicated in the past by interference from a Rieske-type binuclear (2Fe-2S) cluster...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00069a017
更新日期:1993-05-11 00:00:00
abstract::Cyclic AMP receptor protein is involved in the regulation of more than 20 genes. A step in the mechanism of activation of transcription is to induce a significant bending of the DNA upon complex formation between specific DNA and the protein. The induced DNA bending and a structure of the protein-DNA complex were stud...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00137a011
更新日期:1992-06-09 00:00:00
abstract::In human glutathione transferase (GST) A1-1, the C-terminal region covers the active site and contributes to substrate binding. This region is flexible, but upon binding of an active-site ligand, it is stabilized as an amphipatic alpha-helix. The stabilization has implications for the catalytic activity of the enzyme....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991482y
更新日期:1999-12-07 00:00:00
abstract::The fibrillation of misfolded neurodegenerative disease-related proteins has been extensively studied over the past few decades, but the initial oligomerization has been rarely examined even though some recent evidence indicated that small protein oligomers are more neurotoxic than long protein fibers. It is rather di...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b00966
更新日期:2017-12-19 00:00:00
abstract::Apo horse spleen ferritin (apo HoSF) was reconstituted to various core sizes (100-3500 Fe3+/HoSF) by depositing Fe(OH)3 within the hollow HoSF interior by air oxidation of Fe2+. Fe2+ and phosphate (Pi) were then added anaerobically at a 1:4 ratio, and both Fe2+ and Pi were incorporated into the HoSF cores. The resulti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982727u
更新日期:1999-05-18 00:00:00
abstract::Calculations of the electrostatic potentials were made around yeast elongator phenylalanine, aspartate tRNAs, and yeast initiator methionine tRNA in aqueous solution at physiological ionic strength. The calculations were carried out with a finite difference algorithm for solving the nonlinear Poisson-Boltzmann equatio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00454a006
更新日期:1990-01-16 00:00:00
abstract::The molecular chaperone SecB binds to hydrophobic sections of unfolded secretory proteins and thereby prevents their premature folding prior to secretion by the translocase of Escherichia coli. Here, we have investigated the effect of the single-residue mutation of leucine 42 to arginine (L42R) centrally positioned in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi902051e
更新日期:2010-03-23 00:00:00
abstract::Protein misfolding due to missense mutations is a common pathogenic mechanism in cystathionine β-synthase (CBS) deficiency. In our previous studies, we successfully expressed, purified, and characterized nine CBS mutant enzymes containing the following patient mutations: P49L, P78R, A114V, R125Q, E176K, R266K, P422L, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi300435e
更新日期:2012-06-12 00:00:00
abstract::Heparin decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor as a result of its strong binding to the enzyme. Here, we used the slow-binding kinetic approach to decide whether the enzyme-inhibitor interaction proceeds via a two-step mechanism and to identify the step that is affected...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00086a031
更新日期:1993-09-07 00:00:00
abstract::A crude in vitro system which initiates chloroplast DNA synthesis near the D-loop site mapped by electron microscopy [Wu, M., Lou, J. K., Chang, D. Y., Chang, C. H., & Nie, Z. Q. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 6761-6765] consists of soluble proteins and proteins extracted from purified thylakoid membrane. In...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00218a034
更新日期:1991-01-29 00:00:00
abstract::Resonance Raman and UV-visible absorption spectra show that nickel(II) microperoxidase-11 (NiMP-11) is four-coordinate in aqueous solution in the pH range from 1.0 to 13.0. In aqueous solutions of NiMP-11 in the absence of cetyltrimethylammonium bromide (CTAB), NiMP-11 is aggregated. In CTAB micellar solutions, where ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982332a
更新日期:1999-03-02 00:00:00
abstract::Kinases play a critical role in cellular signaling and are dysregulated in a number of diseases, such as cancer, diabetes, and neurodegeneration. Therapeutics targeting kinases currently account for roughly 50% of cancer drug discovery efforts. The ability to explore human kinase biochemistry and biophysics in the lab...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b01081
更新日期:2018-08-07 00:00:00
abstract::The conformations of melittin, an amphipathic polypeptide consisting of 26 amino acid residues, and its hydrophobic (residues 1--19) and hydrophilic (residues 20--26) fragments were examined in various solvent systems, including H2O, 2H2O, 2-chloroethanol, and 1,2-dimyristoylphosphatidylcholine (DMPC) multilayers, by ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00539a006
更新日期:1982-05-11 00:00:00
abstract::Synthetic photocontrolled proteins could be powerful tools for probing cellular chemistry. Several previous attempts to produce such systems by incorporating photoisomerizable chromophores into biomolecules have led to photocontrol but with incomplete reversibility, where the chromophore becomes trapped in one photois...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060142r
更新日期:2006-05-16 00:00:00
abstract::Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme operating in the gluconeogenesis and glyceroneogenesis pathways. Previous work has demonstrated that the enzyme cycles between a catalytically inactive open state and a catalytically active closed state. The transition of the enzyme between the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b01215
更新日期:2016-01-26 00:00:00
abstract::The rigor complexes that formed between rabbit skeletal muscle F-actin and chicken gizzard heavy meromyosin (HMM), in which the heavy chains had been cleaved with trypsin into 24K, 50K, and 68K fragments, were examined by using the zero-length chemical cross-linker 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC)...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00430a070
更新日期:1989-02-21 00:00:00
abstract::Matrix metalloproteinases (MMPs) are a family of enzymes that are up-regulated in many diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). Here we report on a novel technique that can be used to simultaneously measure activity levels for a panel of enzymes, such as the MMPs. The technique, termed th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi036063m
更新日期:2004-03-23 00:00:00
abstract::The effect of DnaB helicase on the initiation specificity of primase was studied biochemically using a series of single-stranded DNA templates in which each nucleotide of the trinucleotide d(CTG) initiation sequence was systematically varied. DnaB helicase accelerated the rate of primer syntheisis, prevented "overlong...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991555d
更新日期:2000-02-01 00:00:00
abstract::Pulsed electron paramagnetic resonance spectroscopy has been used to detect Mn(II)-ligand superhyperfine couplings in complexes with creatine kinase and in the Mn(II) metalloprotein concanavalin A. Electron spin-echo envelopes from Mn(II), bound in these complexes, are modulated by superhyperfine interactions between ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00367a046
更新日期:1986-09-23 00:00:00
abstract::Complement components C5b-6 and C7 assemble to form C5b-7, which then interacts with membranes and commits the membrane attack complex to a target site. This protein-membrane association event was investigated to determine possible structural features that could contribute to a selective membrane attack. This system m...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00371a065
更新日期:1986-11-18 00:00:00
abstract::Vibrational frequencies associated with FeC and CO stretching and FeCO bending modes have been determined via resonance Raman (RR) and infrared (IR) spectroscopy for cytochrome c peroxidase (CCP) mutants prepared by site-directed mutagenesis. These include the bacterial "wild type", CCP(MI), and mutations involving gr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00415a015
更新日期:1988-07-26 00:00:00