A5012894800- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Receptor Mechanisms and Signaling
- Retinal Development and Disorders
- Retinoids in leukemia and cellular processes
- Advanced Thermodynamics and Statistical Mechanics
- stochastic dynamics and bifurcation
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Molecular Sensors and Ion Detection
- Endoplasmic Reticulum Stress and Disease
- Statistical Mechanics and Entropy
- Ubiquitin and proteasome pathways
- Mechanical and Optical Resonators
- Curcumin's Biomedical Applications
- Calcium signaling and nucleotide metabolism
- Alkaloids: synthesis and pharmacology
- Nonlinear Dynamics and Pattern Formation
- Protein Interaction Studies and Fluorescence Analysis
- Neurobiology and Insect Physiology Research
- Computational Drug Discovery Methods
- Photochromic and Fluorescence Chemistry
- Sirtuins and Resveratrol in Medicine
- Toxin Mechanisms and Immunotoxins
University of Houston
2016-2025
Visva-Bharati University
2017-2024
Massachusetts General Hospital
2006-2012
University of Southern California
2011
Stanford University
2011
The University of Texas at Austin
2011
Salk Institute for Biological Studies
2011
Medical University of South Carolina
1999-2007
Massachusetts Institute of Technology
2007
Harvard University
2004-2006
µ-Opioid receptors are pivotal in mediating the analgesic and addictive properties of opioid drugs. (−)-Mitragynine, a natural alkaloid, is known for its effects functions as G protein-biased ligand at µ-opioid receptor. However, molecular-level understanding receptor-mitragynine interactions remains unclear. This study examined structural alterations receptor upon binding with (−)-mitragynine, (+)-mitragynine, 7-OH-mitragynine, morphine using molecular docking 1 µs classical all-atom...
Alcohols regulate the expression and function of PKC (protein kinase C), it has been proposed that an alcohol-binding site is present in alpha its C1 domain, which consists two cysteine-rich subdomains, C1A C1B. A epsilon-knockout mouse showed a significant decrease alcohol consumption compared with wild-type. The aim study was to investigate whether could be epsilon. Here we show ethanol inhibited epsilon activity concentration-dependent manner EC50 (equilibrium ligand concentration at...
Protein kinase C (PKC) is an important signal transduction protein that has been proposed to interact with general anesthetics at its cysteine-rich diacylglycerol/phorbol ester-binding domain C1, a tandem repeat of C1A and C1B subdomains. To test this hypothesis, we expressed, purified, characterized the high affinity phorbol-binding subdomain, C1B, mouse Cδ, studied interaction anesthetic alcohols. When fluorescent phorbol ester, sapintoxin-D, bound PKCδ in buffer molar ratio 1:2,...
Although inflammatory pathways have been linked with various chronic diseases including cancer, identification of an agent that can suppress these has therapeutic potential. Herein we describe the a novel compound bharangin, diterpenoid quinonemethide pro-inflammatory specifically. We found bharangin suppresses nuclear factor (NF)-κB activation induced by cytokine, tumor promoter, cigarette smoke, and endotoxin. Inhibition NF-κB was mediated through suppression phosphorylation degradation...
Munc13-1 is a pre-synaptic active-zone protein essential for neurotransmitter release and involved in plasticity brain. Ethanol, butanol, octanol quenched the intrinsic fluorescence of C1 domain with EC₅₀ s 52 mM, 26 0.7 respectively. Photoactive azialcohols photolabeled exclusively at Glu-582, which was identified by mass spectrometry. Mutation Glu-582 to alanine, leucine, histidine reduced alcohol binding two- five-fold. Circular dichroism studies suggested that increased stability...
PKC (protein kinase C) θ is predominantly expressed in T-cells and critically involved immunity. Design of PKCθ-selective molecules to manage autoimmune disorders by targeting its activator-binding C1 domain requires the knowledge structure residues. The consists twin domains, C1A C1B, which C1B plays a critical role membrane translocation activation PKCθ. In present study we determined crystal PKCθC1B 1.63 Å (1 Å=0.1 nm) resolution, showed that Trp253 at rim pocket was orientated towards...
Bacteriorhodopsin analogues BR−I, BR−II and BR−III containing azo chromophores 4-[[4'-(N,N-dimethylamino)phenyl-1']azo]benzaldehyde, 3-[4-[[4'-(N,N-dimethylamino)phenyl-1']azo]phenyl-1]prop-2-enal 3-[4-[[4'-(N,N-dimethylamino)phenyl-1']azo]phenyl-1]-2-methylprop-2-enal, respectively, were prepared characterized by UV−vis spectroscopy, opsin shift, competitive binding with retinal, fluorescence light-induced pH change, flash photolysis. BR−II, had absorption maxima at 458, 597, 485 nm shifts...
In rhodopsin, the 9-methyl group of retinal has previously been identified as being critical in linking ligand isomerization with subsequent protein conformational changes that result activation its G protein, transducin. Here, we report studies on role this methyl salamander rod and cone pigments. Pigments were generated by combining proteins expressed COS cells 11-cis 9-demethyl retinal, where polyene chain deleted. The absorption spectra all pigments blue-shifted. red blue cone/green...
The visual pigment from the ultraviolet (UV) cone photoreceptor of tiger salamander has been cloned, expressed, and characterized. cDNA contains a full-length open reading frame encoding 347 amino acids. phylogenetic analysis indicates that highest sequence homology is to pigments in S group. UV opsin was tagged at carboxy-terminus with for 1D4 epitope. This fusion expressed COS-1 cells, regenerated 11- cis retinal (A1) immuno-purified, yielding an absorbance maximum (λ max ) 356 nm which...
Protein kinase C (PKC) is an important signal transduction protein whose cysteine-rich regulatory domain C1 has been proposed to interact with general anesthetics in both of its diacylglycerol/phorbol ester-binding subdomains, the tandem repeats C1A and C1B. Previously, we identified allosteric binding site on one two domains, PKCdelta To test hypothesis that there additional anesthetic other subdomain, C1A, subcloned, expressed Escherichia coli, purified, characterized mouse C1A. Octanol...
Resveratrol (1) is a naturally occurring phytoalexin that affects variety of human disease models, including cardio- and neuroprotection, immune regulation, cancer chemoprevention. One the possible mechanisms by which resveratrol these states affecting cellular signaling network involving protein kinase C (PKC). PKC family serine/threonine kinases, whose activity inhibited resveratrol. To develop isotype selective molecules on scaffold, several analogs (2-5) with long aliphatic chain varying...
C1 domains are small zinc-binding structural units of approximately 50 amino acids, originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. that bind and respond to the DAG/phorbol ester termed typical, those do not atypical. To design molecules targeting a specific domain for regulating disease state, it is important understand factors make responsive ester. Here, we determined volume surface area ligand-binding site all known domains. No correlation was found...
Abstract Ethanol has robust effects on presynaptic activity in many neurons, however, it is not yet clear how this drug acts within compartment to change neural activity, nor the significance of behavior and physiology vivo . One possible effector for ethanol Munc13-1 protein. Herein, we show that binding rat C1 domain, at concentrations consistent with binge exposure, reduces diacylglycerol (DAG) binding. The inhibition DAG predicted reduce release. In Drosophila , sedating significantly...
In the present study, we have proposed Fokker-Planck equation in a simple way for Langevin of motion having ordinary derivative (OD), Gaussian random force and generalized frictional memory kernel. The may be associated with or without conservative field from harmonic potential. We extend this method charged Brownian particle presence magnetic field. Thus, is applicable OD, colored thermal noise any kind linear that not. It also to apply not related damping strength.
Curcumin is a polyphenolic nutraceutical that acts on multiple biological targets, including protein kinase C (PKC). PKC family of serine/threonine kinases central to intracellular signal transduction. We have recently shown curcumin selectively inhibits PKCα, but not PKCε, in CHO-K1 cells [Pany, S. (2016) Biochemistry 55, 2135-2143]. To understand which domain(s) PKCα responsible for binding and inhibitory activity, we made several domain-swapped mutants the C1 (combination C1A C1B) C2...