Effect of β,γ-CHF- and β,γ-CHCl-dGTP halogen atom stereochemistry on the transition state of DNA polymerase β.


:Recently, we synthesized the first individual β,γ-CHX-dGTP diastereomers [(R)- or (S)-CHX, where X is F or Cl] and determined their structures in ternary complexes with DNA polymerase β (pol β). We now report stereospecificity by pol β on the mixed β,γ-CHX diastereomer pairs using nuclear magnetic resonance and on the separate diastereomers using transient kinetics. For both the F and Cl diastereomers, the R isomer is favored over the S isomer for G·C correct incorporation, with stereospecificities [(k(pol)/K(d))(R)/(k(pol)/K(d))(S)] of 3.8 and 6.3, respectively, and also for G·T misincorporation, with stereospecificities of 11 and 7.8, respectively. Stereopreference for the (R)-CHF-dGTP diastereomer was abolished for k(pol) but not K(d) with mutant pol β (R183A). These compounds constitute a new class of stereochemical probes for active site interactions involving halogen atoms. As Arg183 is unique in family X pols, the design of CXY deoxyribonucleotide analogues to enhance interaction is a possible strategy for inhibiting BER selectively in cancer cells.






Oertell K,Wu Y,Zakharova VM,Kashemirov BA,Shock DD,Beard WA,Wilson SH,McKenna CE,Goodman MF




Has Abstract


2012-10-30 00:00:00












  • Role of the C-terminus of the high-conductance calcium-activated potassium channel in channel structure and function.

    abstract::The role of ion channels in cell physiology is regulated by processes occurring after protein biosynthesis, which are critical for both channel function and targeting of channels to appropriate cell compartments. Here we apply biochemical and electrophysiological methods to investigate the role of the high-conductance...


    pub_type: 杂志文章


    authors: Schmalhofer WA,Sanchez M,Dai G,Dewan A,Secades L,Hanner M,Knaus HG,McManus OB,Kohler M,Kaczorowski GJ,Garcia ML

    更新日期:2005-08-02 00:00:00

  • Proton nuclear magnetic resonance investigation of cross-linked asymmetrically modified hemoglobins: influence of the salt bridges on tertiary and quaternary structures of hemoglobin.

    abstract::Asymmetrically modified hemoglobins, [alpha(des-Arg)beta]A[alpha beta]cXL, [alpha(des-Arg-Tyr)beta]A[alpha beta]cXL, [alpha(des-Arg)beta(NES)]A[alpha beta]cXL, and [alpha(des-Arg)beta]A[alpha beta(NES)]cXL, have been prepared from chemically modified human normal adult hemoglobin (Hb A) and mutant hemoglobin C (beta 6...


    pub_type: 杂志文章


    authors: Miura S,Ho C

    更新日期:1984-05-22 00:00:00

  • Holo Structure and Steady State Kinetics of the Thiazolinyl Imine Reductases for Siderophore Biosynthesis.

    abstract::Thiazolinyl imine reductases catalyze the NADPH-dependent reduction of a thiazoline to a thiazolidine, a required step in the formation of the siderophores yersiniabactin (Yersinia spp.) and pyochelin (Pseudomonas aeruginosa). These stand-alone nonribosomal peptide tailoring domains are structural homologues of sugar ...


    pub_type: 杂志文章


    authors: Meneely KM,Ronnebaum TA,Riley AP,Prisinzano TE,Lamb AL

    更新日期:2016-09-27 00:00:00

  • An electron-electron double-resonance study of interactions between [14N]- and [15N]stearic acid spin-label pairs: lateral diffusion and vertical fluctuations in dimyristoylphosphatidylcholine.

    abstract::Vertical fluctuations of the terminal methyl groups of stearic acid acyl chains toward the surface of dimyristoylphosphatidylcholine (DMPC) bilayers have been investigated by using spin-label electron-electron double-resonance ( ELDOR ) methodology. Spin-label pairs consisting of two populations of stearic acid spin-l...


    pub_type: 杂志文章


    authors: Feix JB,Popp CA,Venkataramu SD,Beth AH,Park JH,Hyde JS

    更新日期:1984-05-08 00:00:00

  • Mapping of peroxyl radical induced damage on genomic DNA.

    abstract::We have examined the DNA damage produced by reaction of peroxyl radicals with human fibroblast DNA. DNA damage consisted of both strand breaks and base modifications. The extent of strand breaks and base modifications induced as a function of peroxyl radical concentration was determined by quantitation of fragment siz...


    pub_type: 杂志文章


    authors: Rodriguez H,Valentine MR,Holmquist GP,Akman SA,Termini J

    更新日期:1999-12-14 00:00:00

  • Characterization and purification of the monoamine transporter of bovine chromaffin granules.

    abstract::The monoamine transporter of the chromaffin granule membranes can be specifically labeled by the photoaffinity reagent 7-azido-8-[125I]iodoketanserin. The characteristics of the labeled protein have been investigated. Two-dimensional gel electrophoresis of the labeled membranes indicated a MW of about 70,000 and an is...


    pub_type: 杂志文章


    authors: Isambert MF,Gasnier B,Botton D,Henry JP

    更新日期:1992-02-25 00:00:00

  • Characterization of a synthetic peptide corresponding to a receptor binding domain of mouse interferon gamma.

    abstract::A receptor binding region of mouse interferon gamma (IFN gamma) has previously been localized to the N-terminal 39 amino acids of the molecule by use of synthetic peptides and monoclonal antibodies. In this report, a detailed analysis of the synthetic peptide corresponding to this region, IFN gamma (1-39), is presente...


    pub_type: 杂志文章


    authors: Magazine HI,Johnson HM

    更新日期:1991-06-11 00:00:00

  • Solvent interaction of a Hsp70 chaperone substrate-binding domain investigated with water-NOE NMR experiments.

    abstract::The interaction of solvent of the substrate binding domain of the bacterial heat shock 70 chaperone protein DnaK was studied in its apo form and with bound hydrophobic substrate peptide, using refined nuclear magnetic resonance experiments. Distinct differences between the two states of the protein were observed. Acco...


    pub_type: 杂志文章


    authors: Cai S,Stevens SY,Budor AP,Zuiderweg ER

    更新日期:2003-09-30 00:00:00

  • Binding analysis of 1alpha- and 17alpha-dihydrotestosterone derivatives to homodimeric sex hormone-binding globulin.

    abstract::Binding studies of the interaction of immobilized 1alpha- and 17alpha-aminoalkyl derivatives of 5alpha-dihydrotestosterone (DHT) with purified N-deglycosylated homodimeric human sex hormone-binding globulin (SHBG) were performed using a surface plasmon resonance biosensor. These 1alpha- and 17alpha-derivatives with sp...


    pub_type: 杂志文章


    authors: Metzger J,Schnitzbauer A,Meyer M,Söder M,Cuilleron CY,Hauptmann H,Huber E,Luppa PB

    更新日期:2003-11-25 00:00:00

  • DNA minor groove adducts formed by a platinum-acridine conjugate inhibit association of tata-binding protein with its cognate sequence.

    abstract::PT-ACRAMTU ([PtCl(en)(ACRAMTU-S)](NO(3))(2), en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a cytotoxic platinum-acridine conjugate previously shown to form adducts with the N3 endocyclic nitrogen of adenine in the DNA minor groove. This unusual observation and our prior det...


    pub_type: 杂志文章


    authors: Budiman ME,Bierbach U,Alexander RW

    更新日期:2005-08-23 00:00:00

  • A method for the separation of hybrids of chromatographically identical oligomeric proteins. Use of 3,4,5,6-tetrahydrophthaloyl groups as a reversible "chromatographic handle".

    abstract::Hybridization experiments with variants of an oligomeric protein often provide important information regarding subunit structure, function, and interactions. In some systems, however, the variants are so similar electrophoretically and chromatographically that purification of individual hybrids is not feasible. Theref...


    pub_type: 杂志文章


    authors: Gibbons I,Schachman HK

    更新日期:1976-01-13 00:00:00

  • The C-terminal lipid-binding domain of apolipoprotein E is a highly efficient mediator of ABCA1-dependent cholesterol efflux that promotes the assembly of high-density lipoproteins.

    abstract::This study was undertaken to identify the alpha-helical domains of human apoE that mediate cellular cholesterol efflux and HDL assembly via ATP-binding cassette transporter A1 (ABCA1). The C-terminal (CT) domain (residues 222-299) of apoE was found to stimulate ABCA1-dependent cholesterol efflux in a manner similar to...


    pub_type: 杂志文章


    authors: Vedhachalam C,Narayanaswami V,Neto N,Forte TM,Phillips MC,Lund-Katz S,Bielicki JK

    更新日期:2007-03-13 00:00:00

  • Essential role of tyrosine 229 of the oxaloacetate decarboxylase beta-subunit in the energy coupling mechanism of the Na(+) pump.

    abstract::The membrane-bound beta-subunit of oxaloacetate decarboxylase from Klebsiella pneumoniae catalyzes the decarboxylation of carboxybiotin, which is coupled to Na(+) translocation and consumes a periplasmically derived proton. Upon site-directed mutagenesis of 20 polar and/or conserved residues within putative membrane-i...


    pub_type: 杂志文章


    authors: Jockel P,Schmid M,Choinowski T,Dimroth P

    更新日期:2000-04-18 00:00:00

  • Bovine H10 histone subfractions contain an invariant sequence which matches histones H5 rather than H1.

    abstract::Histone H10 differs substantially from H1 in a 37-residue region of the primary structure that is conserved between the usual H1 histones of fish and mammals. Instead, H10 is homologous to H5 in this region. Histones H10 and H5 might be classified together in a histone category distinct from the usual H1. ...


    pub_type: 杂志文章


    authors: Pehrson JR,Cole RD

    更新日期:1981-04-14 00:00:00

  • Coordinating role of His216 in MgATP binding and cleavage in pyruvate carboxylase.

    abstract::His216 is a well-conserved residue in pyruvate carboxylases and, on the basis of structures of the enzyme, appears to have a role in the binding of MgATP, forming an interaction with the 3'-hydroxyl group of the ribose ring. Mutation of this residue to asparagine results in a 9-fold increase in the Km for MgATP in its...


    pub_type: 杂志文章


    authors: Adina-Zada A,Jitrapakdee S,Wallace JC,Attwood PV

    更新日期:2014-02-18 00:00:00

  • Interactions of soluble penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus with moenomycin.

    abstract::Kinetics studies in homogeneous aqueous solution showed that solubilized penicillin-binding protein 2a (sPBP2a) of methicillin-resistant Staphylococcus aureus (a bacterial DD-peptidase) was inhibited by the amphiphilic glycolipid antibiotic moenomycin. Inhibition at the peptidase site was determined by competition exp...


    pub_type: 杂志文章


    authors: Graves-Woodward K,Pratt RF

    更新日期:1999-08-10 00:00:00

  • Observations on the pyridoxal 5'-phosphate inhibition of DNA polymerases.

    abstract::Pyridoxal 5'-phosphate at concentrations greater than 0.5 mM inhibits polymerization of deoxynucleoside triphosphate catalyzed by a variety of DNA polymerases. The requirement for a phosphate as well as aldehyde moiety of pyridoxal phosphate for inhibition to occur is clearly shown by the fact that neither pyridoxal n...


    pub_type: 杂志文章


    authors: Modak MJ

    更新日期:1976-08-10 00:00:00

  • Influence of the calcium-induced gel phase on the behavior of small molecules in phosphatidylserine and phosphatidylserine-phosphatidylcholine multilamellar vesicles.

    abstract::The behavior of fluorescent and spin-label probes is examined in several fluid and gel phospholipid phases, with particular focus on the Ca2+-induced gel phase in phosphatidylserine (PS). These probes have behavior characteristic of the type of probe and of the type of lipid environment. Anthroyloxy- and doxyl-labeled...


    pub_type: 杂志文章


    authors: Florine KI,Feigenson GW

    更新日期:1987-03-24 00:00:00

  • The catalytic mechanism of kynureninase from Pseudomonas fluorescens: evidence for transient quinonoid and ketimine intermediates from rapid-scanning stopped-flow spectrophotometry.

    abstract::The reaction of Pseudomonas fluorescens kynureninase with L-kynurenine and L-alanine has been examined using rapid-scanning stopped-flow spectrophotometry. Mixing kynureninase with 0.5 mM L-kynurenine results in formation of a quinonoid intermediate, with lambdamax = 494 nm, within the dead time (ca. 2 ms) of the stop...


    pub_type: 杂志文章


    authors: Phillips RS,Sundararaju B,Koushik SV

    更新日期:1998-06-16 00:00:00

  • Tubulin Binding and Polymerization Promoting Properties of Tubulin Polymerization Promoting Proteins Are Evolutionarily Conserved.

    abstract::Tubulin polymerization promoting proteins (TPPPs) constitute a eukaryotic protein family. There are three TPPP paralogs in the human genome, denoted as TPPP1-TPPP3. TPPP1 and TPPP3 are intrinsically unstructured proteins (IUPs) that bind and polymerize tubulin and stabilize microtubules, but TPPP2 does not. Vertebrate...


    pub_type: 杂志文章


    authors: Oláh J,Szénási T,Szabó A,Kovács K,Lőw P,Štifanić M,Orosz F

    更新日期:2017-02-21 00:00:00

  • Disentangling the coil: modulation of conformational and dynamic properties by site-directed mutation in the non-native state of hen egg white lysozyme.

    abstract::The conformational analysis of non-native states of proteins remains one of the most difficult problems in structural biology, because such states are represented by a superimposition of several states that are rapidly interconverting. Hence, model building of the conformational ensemble remains challenging, although ...


    pub_type: 杂志文章


    authors: Sziegat F,Silvers R,Hähnke M,Jensen MR,Blackledge M,Wirmer-Bartoschek J,Schwalbe H

    更新日期:2012-04-24 00:00:00

  • Effect of Different Divalent Cations on the Kinetics and Fidelity of RB69 DNA Polymerase.

    abstract::Although Mg(2+) is the cation that functions as the cofactor for the nucleotidyl transfer reaction for almost all DNA polymerases, Mn(2+) can also serve, but when it does, the degree of base discrimination exhibited by most DNA polymerases (pols) is diminished. Metal ions other than Mg(2+) or Mn(2+) can also act as co...


    pub_type: 杂志文章


    authors: Vashishtha AK,Konigsberg WH

    更新日期:2016-05-10 00:00:00

  • Transformation of the CuA redox site in cytochrome c oxidase into a mononuclear copper center.

    abstract::Subunit II of the aa3 type cytochrome c oxidase contains a binuclear copper center (CuA) which functions as the entry point for electrons donated by cytochrome c. We have introduced site-specific mutations in residues liganding the CuA center in the oxidase of the bacterium Paracoccus denitrificans; the purified, full...


    pub_type: 杂志文章


    authors: Zickermann V,Wittershagen A,Kolbesen BO,Ludwig B

    更新日期:1997-03-18 00:00:00

  • Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines: evidence for a novel regulatory mechanism.

    abstract::The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the affinities of catechols have been determined with both the ferric and ferrous forms of the enzyme. Phosphorylation had no effect on the Ki value for the inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate of turnov...


    pub_type: 杂志文章


    authors: Ramsey AJ,Fitzpatrick PF

    更新日期:1998-06-23 00:00:00

  • Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e.

    abstract::Five previously unknown hemorrhagic proteins, designated hemorrhagic toxins a,b,c,d, and e, were isolated from the venom of the western diamondback rattlesnake (Crotalus atrox). Molecular weights of hemorrhagic toxins a-e were determined to be 68 000, 24 000, 24 000, 24 000, and 25 700, respectively, by sodium dodecyl...


    pub_type: 杂志文章


    authors: Bjarnason JB,Tu AT

    更新日期:1978-08-08 00:00:00

  • Sum of the parts: mass spectrometry-based metabolomics.

    abstract::Metabolomics is a rapidly growing field of research used in the identification and quantification of the small molecule metabolites within an organism, thereby providing insights into cell metabolism and bioenergetics as well as processes important in clinical medicine, such as disposition of pharmaceutical compounds....


    pub_type: 杂志文章,评审


    authors: Milne SB,Mathews TP,Myers DS,Ivanova PT,Brown HA

    更新日期:2013-06-04 00:00:00

  • The sigma enigma: in vitro/in silico site-directed mutagenesis studies unveil σ1 receptor ligand binding.

    abstract::The σ1 receptor is an integral membrane protein that shares no homology with other receptor systems, has no unequivocally identified natural ligands, but appears to play critical roles in a wide variety of cell functions. While the number of reports of the possible functions of the σ1 receptor is increasing, almost no...


    pub_type: 杂志文章


    authors: Brune S,Schepmann D,Klempnauer KH,Marson D,Dal Col V,Laurini E,Fermeglia M,Wünsch B,Pricl S

    更新日期:2014-05-13 00:00:00

  • Inhibition of gene expression and cell proliferation by triple helix-forming oligonucleotides directed to the c-myc gene.

    abstract::Triple helix-forming oligonucleotides (TFOs) bind with high affinity and specificity to homopurine-homopyrimidine sequences in DNA and have been shown to inhibit transcription of target genes in various experimental systems. In the present study, we evaluated the ability of 3'-amino-modified phosphodiester TFOs direct...


    pub_type: 杂志文章


    authors: Catapano CV,McGuffie EM,Pacheco D,Carbone GM

    更新日期:2000-05-02 00:00:00

  • Targeted cleavage of polynucleotides by complementary oligonucleotides covalently linked to iron-porphyrins.

    abstract::Oligothymidylates covalently linked to iron-porphyrins were synthesized to target the nuclease activity of Fe-porphyrin to complementary polynucleotides. In the presence of oxygen and a reducing agent, oligo(dT)7 bearing the reactive group attached to the 3'-phosphate was shown to be active in the cleavage of poly(dA)...


    pub_type: 杂志文章


    authors: Le Doan T,Perrouault L,Helene C,Chassignol M,Thuong NT

    更新日期:1986-11-04 00:00:00

  • Electrophoretic mobility is a reporter of hairpin structure in single-stranded DNA oligomers.

    abstract::The electrophoretic mobilities of 24 single-stranded DNA oligomers, each containing 26 nucleotide residues, have been measured in polyacrylamide gels and in free solution. The mobilities observed at 20 degrees C differed by approximately 20% in polyacrylamide gels and by approximately 10% in free solution, even though...


    pub_type: 杂志文章


    authors: Stellwagen E,Abdulla A,Dong Q,Stellwagen NC

    更新日期:2007-09-25 00:00:00