A5075994602- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- Electron Spin Resonance Studies
- Biochemical Analysis and Sensing Techniques
- Neurological diseases and metabolism
- Regulation of Appetite and Obesity
- Chemical Synthesis and Analysis
- Alzheimer's disease research and treatments
- melanin and skin pigmentation
- Spectroscopy and Quantum Chemical Studies
- DNA and Nucleic Acid Chemistry
- Receptor Mechanisms and Signaling
- Molecular spectroscopy and chirality
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Peptides and Activities
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Electrochemical Analysis and Applications
- Ion channel regulation and function
- Molecular Junctions and Nanostructures
- Crystallography and molecular interactions
- Amino Acid Enzymes and Metabolism
- Nitric Oxide and Endothelin Effects
University of California, Santa Cruz
2016-2025
National Bureau of Economic Research
2021
Tulane University
2021
University of California System
2014-2020
University of California, Berkeley
2017
Santa Cruz County Office of Education
2014
University College London
2013
Centre National de la Recherche Scientifique
2010
National High Magnetic Field Laboratory
2010
Bruker (United States)
2010
Little is known about the effect of conformation on passive membrane diffusion rates in small molecules. Evidence suggests that intramolecular hydrogen bonding may play a role by reducing energetic cost desolvating bond donors, especially amide N−H groups. We set out to test this hypothesis investigating characteristics series cyclic peptide diastereomers based sequence cyclo[Leu-Leu-Leu-Leu-Pro-Tyr]. identified two hexapeptide sequence, whose differed nearly log units. Results solution NMR...
Recent evidence suggests that the prion protein (PrP) is a copper binding protein. The N-terminal region of human PrP contains four sequential copies highly conserved octarepeat sequence PHGGGWGQ spanning residues 60−91. This selectively binds Cu2+ in vivo. In previous study using peptide design, EPR, and CD spectroscopy, we showed HGGGW segment within each comprises fundamental unit [Aronoff-Spencer et al. (2000) Biochemistry 40, 13760−13771]. Here present first atomic resolution view site...
α-Synuclein (SNCA) is central to the pathogenesis of Parkinson disease (PD), with 3 missense mutations reported date. We report a novel mutation (p.H50Q) in pathologically proven case.
Genetic analysis of mammalian color variation has provided fundamental insight into human biology and disease. In most vertebrates, two key genes, Agouti Melanocortin 1 receptor ( Mc1r ), encode a ligand-receptor system that controls pigment type-switching, but in domestic dogs, third gene is implicated, the K locus, whose genetic characteristics predict previously unrecognized component melanocortin pathway. We identify locus as β- defensin 103 CBD103 ) show its protein product binds with...
The discovery of air-stable n-dopants for organic semiconductor materials has been hindered by the necessity high-energy HOMOs and air sensitivity compounds that satisfy this requirement. One strategy circumventing problem is to utilize stable precursor molecules form active doping complex in situ during process or a postdeposition thermal- photo-activation step. Some us have reported on use 1H-benzimidazole (DMBI) benzimidazolium (DMBI-I) salts as solution- vacuum-processable n-type dopant...
Recent evidence indicates that the prion protein (PrP) plays a role in copper metabolism central nervous system. The N-terminal region of human PrP contains four sequential copies highly conserved octarepeat sequence PHGGGWGQ spanning residues 60-91. This selectively binds divalent ions (Cu(2+)) vivo. To elucidate specific mode and site binding, we have studied series Cu(2+)-peptide complexes composed 1-, 2-, 4-octarepeats several sub-octarepeat peptides, by electron paramagnetic resonance...
The prion protein (PrP) binds divalent copper at physiologically relevant conditions and is believed to participate in regulation or act as a copper-dependent enzyme. Ongoing studies aim determining the molecular features of binding sites. emerging consensus that most octarepeat domain, which composed four more copies fundamental sequence PHGGGWGQ. Previous work from our laboratory using PrP-derived peptides, conjunction with EPR X-ray crystallography, demonstrated HGGGW segment constitutes...
The prion protein (PrP) binds Cu2+ in its N-terminal octarepeat domain. This unusual domain is comprised of four or more tandem repeats the fundamental sequence PHGGGWGQ. Previous work from our laboratories demonstrates that at full copper occupancy, each HGGGW segment a single Cu2+. However, several recent studies suggest low occupancy favors different coordination modes, possibly involving imidazoles histidines adjacent octapeptide segments. investigated here using combination X-band EPR,...
The lifetimes of the unitary currents from ion channels, as revealed single-channel recording, are traditionally thought to follow exponential or multiexponential distributions. interpretation these event-time distributions is that gating process follows Markov kinetics among a small number states. There recent evidence, however, certain systems exhibit power laws functions related laws. Likewise, it has been suggested data sets appear be may fit simple well. In this paper we propose...
ZnO/GQD nanocomposites exhibit markedly enhanced antimicrobial activity under UV photoirradiation as compared to that in ambient room light, due photo-induced generation of reactive oxygen species. The the nanocomposite is also higher than with individual components.
β-Defensins are cationic host defense peptides that form an amphipathic structure stabilized by three intramolecular disulfide bonds. They key players in innate and adaptive immunity have recently been shown to limit the production of pro-inflammatory cytokines TLR4-stimulated macrophages. In present study, we investigate mechanism underlying anti-inflammatory effect human β-defensin 3 (hBD3). We show canonical hBD3 is required for this immunosuppressive rapidly associates with enters...
Some calcium is required for binding The melanocortin-4 receptor (MC4R) coordinates food intake and energy expenditure a target treating obesity. MC4R an unusual G protein–coupled receptor, in part because it binds either endogenous agonist or antagonist, leading to reduced appetite increased intake, respectively. Yu et al. determined the structure of bound antagonist (see Perspective by Chaturvedi Shukla). This revealed ion coordinated antagonist. Biochemical studies showed that also...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTα and 310: The Split Personality of Polypeptide HelicesKimberly A. Bolin Glenn L. MillhauserView Author Information Department Chemistry Biochemistry, University California, Santa Cruz, California 95064 Cite this: Acc. Chem. Res. 1999, 32, 12, 1027–1033Publication Date (Web):September 23, 1999Publication History Received14 June 1999Published online23 September inissue 1 December...
The prion protein (PrP) binds Cu2+ in its N-terminal octarepeat domain, composed of four or more tandem PHGGGWGQ segments. Previous work from our laboratory demonstrates that copper interacts with the domain through three distinct coordination modes at pH 7.4, depending upon precise ratio to protein. Here, we apply both electron paramagnetic resonance (EPR) and fluorescence quenching determine affinity for each these modes. At low occupancy, which favors multiple His coordination, a...
A technique is described for the study of slow molecular motions that employs two-dimensional electron spin echo (2D-ESE) spectroscopy. An ‘‘echo-induced ESR spectrum’’ obtained with a two pulse 90° (τ)/() 180° sequence by recording height as dc field swept. series sweeps different τ are Fourier transformed to yield spectrum comprised an echo-induced along x axis and homogeneous widths y axis. convenient theoretical analysis appropriate given it shown 2D may be regarded graph vs resonance...
PrP binds copper in the highly conserved, unstructured N-terminal half of protein. The octarepeat region consists four tandem repeats PHGGGWGQ and 4 equiv at full occupancy. Adjacent to octarepeats are two additional histidines that may also bind copper. We recently showed that, when is titrated with Cu2+, binding mode depends on number equivalents bound. In addition copper, other metals have been associated PrP; however, zinc only metal than induces endocytosis, inhibits fibril formation,...
Parkinson's disease (PD) is the second most prevalent age-related, neurodegenerative disorder, affecting >1% of population over age 60. PD pathology marked by intracellular inclusions composed primarily protein α-synuclein (α-syn). These also contain copper, and interaction Cu(2+) with α-syn may play an important role in fibrillogenesis. Here we report stoichiometry, affinity, coordination structure Cu(2+)-α-syn complex. Electron paramagnetic resonance (EPR) titrations show that monomeric...