- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- DNA Repair Mechanisms
- HIV Research and Treatment
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Bacterial Genetics and Biotechnology
- RNA Research and Splicing
- Photochemistry and Electron Transfer Studies
- Bacteriophages and microbial interactions
- Spectroscopy and Quantum Chemical Studies
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Chemokine receptors and signaling
- Protein Structure and Dynamics
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- Molecular Junctions and Nanostructures
- Metal complexes synthesis and properties
- HIV/AIDS drug development and treatment
- Electron Spin Resonance Studies
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
Scripps Research Institute
2016-2025
Simon Diedong Dombo University of Business and Integrated Development Studies
2022
Institute of Molecular Biology
2012
North Tyneside General Hospital
2009
Stanford University
2009
California Institute of Technology
1978-2008
Barnard College
2004-2007
Columbia University
1985-2007
Boston University
2007
Chalmers University of Technology
2007
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamics of mismatched base pairs in DNAChristopher R. Guest, Remo A. Hochstrasser, Lawrence C. Sowers, and David P. MillarCite this: Biochemistry 1991, 30, 13, 3271–3279Publication Date (Print):April 2, 1991Publication History Published online1 May 2002Published inissue 2 April 1991https://pubs.acs.org/doi/10.1021/bi00227a015https://doi.org/10.1021/bi00227a015research-articleACS PublicationsRequest reuse permissionsArticle...
Subnanosecond time-resolved fluorescence depolarization has been used to monitor the reorientation of ethidium bromide intercalated in native DNA, synthetic polynucleotide complexes, and supercoiled plasmid DNA. The polarization anisotropy was successfully analyzed with an elastic model DNA dynamics, including both torsion bending, which yielded accurate value for torsional rigidity different samples. dependence on base sequence, helical structure, tertiary structure experimentally observed....
Significance Activation of G protein-coupled receptors (GPCRs) by agonists is the first step eukaryotic cellular signal transduction. Because GPCRs are expressed in almost all human tissues and play a key role physiology, they targets for more than 30% pharmaceutical drugs. Binding ligands on extracellular surface GPCR induces conformational change cytoplasmic surface, which recognized proteins or other effectors. Here we show that β 2 -adrenergic receptor, prototypical GPCR, naturally...
The solvent-dependent ground-state conformational equilibrium and excited-state dynamics of 2-(2'-hydroxyphenyl)benzoxazole have been characterized in several solvents on the femtosecond to nanosecond time scales. only observable tautomer is enol, which exists between syn- anti-rotational isomers. In anti-enol isomer, phenyl hydroxyl group appears not interact strongly with solvent but rather forms a strong intramolecular hydrogen bond benzoxazole oxygen atom. syn-enol proton may or form an...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe nucleotide analog 2-aminopurine as a spectroscopic probe of incorporation by the Klenow fragment Escherichia coli polymerase I and bacteriophage T4 DNA polymeraseMichelle West Frey, Lawrence C. Sowers, David P. Millar, Stephen J. BenkovicCite this: Biochemistry 1995, 34, 28, 9185–9192Publication Date (Print):July 18, 1995Publication History Published online1 May 2002Published inissue 18 July...
Picosecond time-dependent fluorescence depolarization techniques have been used to monitor the reorientation of ethidium bromide intercalated in DNA and RNA. The polarization anisotropy reveals a nonexponential, exp(-at 1/2), torsional relaxation double helix provides an accurate value for its rigidity, C = 1.3 +/- 0.2 X 10(-19) erg cm. Furthermore, from measurements limiting at zero time, we conclude that there is additional fast (< 10 psec) internal motion depends on viscosity medium....
A continuous fluorescence-based assay is described for measuring helicase-mediated unwinding of duplex DNA. The utilizes an oligonucleotide substrate containing the fluorescent adenine analog, 2-aminopurine, at regular intervals. 2-Aminopurine forms a Watson-Crick-type base pair with thymine and does not distort normal B-form Fluorescence 2-aminopurines within this quenched 2-fold upon its hybridization to complementary strand. Unwinding by T4 dda helicase restores fluorescence easily...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformational distributions of a four-way DNA junction revealed by time-resolved fluorescence resonance energy transferPeggy S. Eis and David P. MillarCite this: Biochemistry 1993, 32, 50, 13852–13860Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/bi00213a014https://doi.org/10.1021/bi00213a014research-articleACS PublicationsRequest reuse...
The forte of catalytic antibodies has resided in the control ground-state reaction coordinate. A principle and method are now described which can direct outcome photophysical photochemical events that take place on excited-state potential energy surfaces. key component is a chemically reactive optical sensor provides report dynamic interplay between protein ligand at active site. To illustrate concept, we used trans -stilbene hapten to elicit panel monoclonal displayed range fluorescent...
Accurate synthesis of DNA by polymerase is due in part to the selective removal misincorporated nucleotides a 3'-5' exonuclease activity (proofreading). Proofreading an domain containing single-stranded binding site may involve local melting duplex substrate. Here we use time-resolved fluorescence spectroscopy analyze terminus induced Klenow fragment I. Four oligodeoxynucleotide primer/templates were prepared, each fluorescent adenine analog 2-aminopurine (A*) at primer 3' terminus, and one...
Recombination of genes is essential to the evolution genetic diversity, segregation chromosomes during cell division, and certain DNA repair processes. The Holliday junction, a four-arm, four-strand branched crossover structure, formed as transient intermediate recombination processes in cell. recognition subsequent resolution junctions into parental or recombined products appear be critically dependent on their three-dimensional structure. Complementary NMR time-resolved fluorescence...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of DNA with the Klenow fragment polymerase I studied by time-resolved fluorescence spectroscopyChristopher R. Guest, Remo A. Hochstrasser, Dwayne J. Allen, Stephen Benkovic, David P. Millar, and Charles G. DupuyCite this: Biochemistry 1991, 30, 36, 8759–8770Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September...
Oligomerization of the HIV-1 protein Rev on Response Element (RRE) regulates nuclear export genomic viral RNA and partially spliced mRNAs encoding for structural proteins. Single-molecule fluorescence spectroscopy has been used to dissect multistep assembly pathway this essential ribonucleoprotein, revealing dynamic intermediates mechanism assembly. Assembly is initiated by binding a high-affinity site in stem-loop IIB RRE proceeds rapidly addition single monomers, facilitated cooperative...
Energy transfer between donor and acceptor molecules randomly distributed in condensed phases is investigated by time-resolved spectroscopy on the picosecond nanosecond time scales. The effects of translational diffusion excitation among donors experimentally observed used to test theoretical models based a equation for excitation. data demonstrate that Förster dipole–dipole model valid cresyl violet (donor):azulene (acceptor) system from 1 ps at least 10 ns after excitation, over 1000-fold...
Enzymatic reactions typically involve complex dynamics during substrate binding, conformational rearrangement, chemistry, and product release. The noncovalent steps provide kinetic checkpoints that contribute to the overall specificity of enzymatic reactions. DNA polymerases perform replication with outstanding fidelity by actively rejecting noncognate nucleotide substrates early in reaction pathway. Substrates are delivered active site a flexible fingers subdomain enzyme, as it converts...
The canonical chemokine receptor CXCR4 and atypical ACKR3 both respond to CXCL12 but induce different effector responses regulate cell migration. While couples G proteins directly promotes migration, is protein-independent scavenges extracellular levels maintain responsiveness, thereby indirectly influencing receptors also have distinct activation requirements. only responds wild-type sensitive mutation of the chemokine. By contrast, recruits GPCR kinases (GRKs) β-arrestins promiscuously...
The kinetics of PaeR7 endonuclease-catalysed cleavage reactions fluorophor-labeled oligonucleotide substrates have been examined using fluorescence resonance energy transfer (FRET). A series duplex were synthesized with an internal CTCGAG PaeKl recognition site and donor (fluorescein) acceptor (rhodamine) dyes conjugated to the opposing 5′ termini. time-dependent increase in resulting from restriction these was continuously monitored initial rate data fitted Michaelis - Menten equation....
The rates of optically induced conformational changes excited state 1,1′-binaphthyl in a series alcohol solvents were measured by picosecond laser technique. Excellent agreement with experiment is found for the Kramers model both intermediate and high friction regimes using frequency independent coefficient evaluated from classical hydrodynamics. This first observation behavior regime indicates that deviations not universal phenomenon dynamics flexible molecules solution. It also emphasizes...