A5073513408- Pharmacogenetics and Drug Metabolism
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Photochemistry and Electron Transfer Studies
- Metal-Catalyzed Oxygenation Mechanisms
- Photosynthetic Processes and Mechanisms
- Hemoglobin structure and function
- Spectroscopy and Quantum Chemical Studies
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
- thermodynamics and calorimetric analyses
- Cellular Mechanics and Interactions
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Receptor Mechanisms and Signaling
- Mass Spectrometry Techniques and Applications
- Force Microscopy Techniques and Applications
- Photoreceptor and optogenetics research
- Welding Techniques and Residual Stresses
- Biotin and Related Studies
- Laser Material Processing Techniques
University of Illinois Urbana-Champaign
2012-2024
Urbana University
2019
Goodwin College
2012-2017
University of North Carolina at Chapel Hill
2009
University of California, Davis
1999
Heriot-Watt University
1997-1998
University of Liverpool
1997
University of Arkansas System
1993
University of Houston
1988
Increased affinity of integrins for the extracellular matrix (activation) regulates cell adhesion and migration, assembly, mechanotransduction. Major uncertainties concern sufficiency talin activation, whether conformational change without clustering leads to mechanical force is required molecular extension. Here, we reconstructed physiological integrin activation in vitro used cellular, biochemical, biophysical, ultrastructural analyses show that binding sufficient activate αIIbβ3....
G-protein-coupled receptor (GPCR) oligomerization has been observed in a wide variety of experimental contexts, but the functional significance this phenomenon at different stages life cycle class A GPCRs remains to be elucidated. Rhodopsin (Rh), prototypical GPCR visual transduction, is also capable forming dimers and higher order oligomers. The recent demonstration that Rh monomer sufficient activate its cognate G protein, transducin, prompted us test whether same monomeric state for...
Based on properties of excitatory frequency (spectral) receptive fields (esRFs), previous studies have indicated that cat primary auditory cortex (A1) is composed functionally distinct dorsal and ventral subdivisions. Dorsal A1 (A1d) has been suggested to be involved in analyzing complex spectral patterns, whereas (A1v) appears better suited for narrowband sounds. However, these were based single-tone stimuli did not consider how neuronal responses tones are modulated when the part a more...
The role of lipid domain size and protein−lipid interfaces in the thermotropic phase transition dipalmitoylphosphatidylcholine (DPPC) dimyristoylphosphatidylcholine (DMPC) bilayers Nanodiscs was studied using small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), generalized polarization (GP) lipophilic probe Laurdan. are water-soluble, monodisperse, self-assembled encompassed by a helical membrane scaffold protein (MSP). MSPs different lengths were used to define...
Nanoscale protein supported phospholipid bilayer discs, or Nanodiscs, were produced for the purpose of studying phase transition behavior incorporated lipids. Nanodiscs and vesicles prepared with two phospholipids, dipalmitoyl phosphatidylcholine dimyristoyl phosphatidylcholine, each was analyzed using laurdan fluorescence differential scanning calorimetry. Laurdan is a fluorescent probe sensitive to increase hydration in lipid that accompanies gel liquid crystalline transition. The emission...
The study of membrane proteins and receptors presents many challenges to researchers wishing perform biophysical measurements determine the structure, function, mechanism action such components. In most cases, be fully functional, require presence a native phospholipid bilayer. addition, complex multiprotein assemblies involved in cellular communication an integral protein as well surface for assembly information transfer soluble partners signaling cascade. Incorporation into Nanodiscs...
The cytochrome P450 (CYP) superfamily of heme monooxygenases has demonstrated ability to facilitate hydroxylation, desaturation, sulfoxidation, epoxidation, heteroatom dealkylation, and carbon–carbon bond formation cleavage (lyase) reactions. Seeking study the reaction α-hydroxy ketones in mechanistic detail using a microbial P450, we synthesized ketone probes based on physiological substrate for well-characterized benzoic acid metabolizing CYP199A4. After observing low activity with...
KRAS4b is a small GTPase involved in cellular signaling through receptor tyrosine kinases. The activation of occurs only after recruitment the regulatory proteins to plasma membrane, thus making role phospholipid bilayer an integral part mechanism. Phospholipids, primarily with anionic headgroups, interact both membrane-anchoring hypervariable (HVR) region and G-domain (catalytic domain) influence orientation on membrane surface, potentially playing key regulation activation. Although there...
We developed an efficient and sensitive probe for drug–drug interactions mediated by human CYP3A4 using midazolam (MDZ) as a substrate. Using global analysis of four parameters over several experimental data sets, we demonstrate that the first MDZ molecule (MDZ1) binds with high affinity at productive site near heme iron gives only hydroxylation 1 position (1OH). The second (MDZ2) allosteric membrane surface perturbs mobility MDZ1 such minor product 4 (4OH) is formed in 1:2 ratio (35%). No...
The heme enzymes of the cytochrome P450 superfamily (CYPs) catalyze oxidation reactions with a high level selectivity. Here, CYP199A4 enzyme from bacterium Rhodopseudomonas palustris HaA2 is used to hydroxylation carbonyl-containing compounds generate α-hydroxyketones. Both 4-propionyl- and 4-(2-oxopropyl)-benzoic acids were regioselectively hydroxylated by this α-hydroxyketone metabolites, 4-(2-hydroxypropanoyl)benzoic acid 4-(1-hydroxy-2-oxopropyl)benzoic acid, respectively,...
Integrins are vital transmembrane receptors that mediate cell–cell and cell–extracellular matrix interactions signaling. Talin is a 270 kDa protein considered key regulator of integrin activity. The interaction between talin commonly regarded as the final step inside-out activation. In cytosol, adopts an autoinhibited conformation, in which C-terminal rod domain binds N-terminal head domain, preventing with membrane surface cytoplasmic domain. It has long been suggested presence...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular electron transfer in cytochrome b5 labeled with ruthenium(II) polypyridine complexes: rate measurements the Marcus inverted regionJill R. Scott, Anne Willie, Mark McLean, Patrick S. Stayton, Stephen G. Sligar, Bill Durham, and Francis MillettCite this: J. Am. Chem. Soc. 1993, 115, 15, 6820–6824Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July...
Chromophore assisted laser inactivation (CALI) is a technique that uses irradiation of chromophores proximate to target protein inactivate function. Previously, enhanced green fluorescent (EGFP) mediated CALI has been used EGFP-fusion proteins in spatio-temporally defined manner within cells, but the mechanism unknown.(1, 2) To help elucidate by ([FP]-CALI), activities purified glutathione-S-transferase-FP (GST-EXFP) fusions were measured after vitro. Singlet oxygen and free radical...
Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% current pharmaceuticals and therefore responsible for multiple drug-drug interactions (DDI). In order to develop a method detection prediction possible involvement new drug candidates CYP3A4-mediated DDI, we evaluated application midazolam (MDZ) as probe substrate. MDZ hydroxylated by two positions: 1-hydroxy formed at lower substrate concentrations, up 4-hydroxy high concentrations. The ratio formation rates these...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntracomplex electron transfer between ruthenium-65-cytochrome b5 and position-82 variants of yeast iso-1-cytochrome cAnne Willie, Mark McLean, Rui Qin Liu, Sharon Hilgen-Willis, Aleister J. Saunders, Gary Pielak, Stephen G. Sligar, Bill Durham, Francis MillettCite this: Biochemistry 1993, 32, 29, 7519–7525Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July...