A5083389629- Drug Transport and Resistance Mechanisms
- DNA and Nucleic Acid Chemistry
- Trace Elements in Health
- Lipid Membrane Structure and Behavior
- RNA Interference and Gene Delivery
- Ion channel regulation and function
- Hemoglobinopathies and Related Disorders
- Cardiomyopathy and Myosin Studies
- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Protein Interaction Studies and Fluorescence Analysis
- Neonatal Health and Biochemistry
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Neuroscience and Neural Engineering
- Advanced biosensing and bioanalysis techniques
- Connexins and lens biology
- Muscle Physiology and Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Adenosine and Purinergic Signaling
- HIV/AIDS drug development and treatment
- Protein Structure and Dynamics
- Nanoparticle-Based Drug Delivery
- Pharmacological Effects and Toxicity Studies
- Supramolecular Self-Assembly in Materials
University of California, Merced
2016-2025
Texas Tech University Health Sciences Center
2011-2016
Texas Tech University
2011-2016
University of Massachusetts Chan Medical School
2004-2011
Instituto Venezolano de Investigaciones Científicas
2000-2004
Contraction of the heart results from interaction myosin and actin filaments. Cardiac filaments consist molecular motor II, sarcomeric template protein, titin, cardiac modulatory binding protein C (MyBP-C). Inherited hypertrophic cardiomyopathy (HCM) is a disease caused mainly by mutations in these proteins. The structure alterations HCM are unknown. We have used electron microscopy image analysis to determine three-dimensional wild-type mouse muscle MyBP-C knockout model for HCM....
Myosin-binding protein C (MyBP-C) is a thick filament playing an essential role in muscle contraction, and MyBP-C mutations cause heart skeletal disease millions worldwide. Despite its discovery 40 y ago, the mechanism of function remains unknown. In vitro studies suggest that could regulate contraction unique way—by bridging thin filaments—but there has been no evidence for this vivo. Here we use electron tomography exceptionally well preserved to demonstrate does indeed bind actin intact...
P-glycoprotein (Pgp) is an efflux pump important in multidrug resistance of cancer cells and determining drug pharmacokinetics. Pgp a prototype ATP-binding cassette transporter with two nucleotide-binding domains (NBDs) that bind hydrolyze ATP. Conformational changes at the NBDs (the engines) lead to across transmembrane result substrate translocation. According current alternating access models (substrate-binding pocket accessible only one side membrane time), binding ATP promotes NBD...
Although the role of hydrophilic antioxidants in development hepatic insulin resistance and nonalcoholic fatty liver disease has been well studied, lipophilic remains poorly characterized. A known hydrogen peroxide scavenger is bilirubin, which can be oxidized to biliverdin then reduced back bilirubin by cytosolic reductase. Oxidation inside mitochondria must followed export cytosol, where bilirubin. Thus, putative mitochondrial exporter expected a major determinant regeneration...
Postnatal maturation of the rat heart is characterized by major changes in mechanism excitation-contraction (E-C) coupling. In neonate, t tubules and sarcoplasmic reticulum (SR) are not fully developed yet. Consequently, Ca(2+)-induced Ca(2+) release (CICR) does play a central role E-C most that triggers contraction comes through sarcolemma. this work, we defined contribution sarcolemmal entry released from SR to transient during first 3 wk postnatal development. To end, intracellular...
Lipid nanodiscs have become a widely used approach for studying membrane proteins thanks to several advantages they offer. They been especially useful ABC transporters, despite the growing concern about possible restriction of conformational changes transporters due small size discs. Here, we performed systematic study determine effect nanodisc on ATPase activity model from human, plant, and bacteria. Our data confirm that their response regulatory molecules is affected by size. findings...
Most ATP binding cassette (ABC) proteins are pumps that transport substrates across biological membranes using the energy of hydrolysis. Functional ABC have two nucleotide-binding domains (NBDs) bind and hydrolyze ATP, but molecular mechanism nucleotide hydrolysis is unresolved. This due in part to limited kinetic information on NBD association dissociation. Here, we show dimerization a catalytically active follow real time dissociation NBDs from changes fluorescence emission tryptophan...
ATP-binding cassette (ABC) proteins have two nucleotide-binding domains (NBDs) that work as dimers to bind and hydrolyze ATP, but the molecular mechanism of nucleotide hydrolysis is controversial. In particular, it still unresolved whether leads dissociation ATP-induced or opening dimers, with NBDs remaining in contact during cycle. We studied a prototypical ABC NBD, Methanococcus jannaschii MJ0796, using spectroscopic techniques. show fluorescence from tryptophan positioned at dimer...
Heme biosynthesis occurs through a series of reactions that take place within the cytoplasm and mitochondria, so intermediates need to move across these cellular compartments. However, specific membrane transport mechanisms involved in process are not yet identified. The ATP-binding cassette protein ABCB10 is essential for normal heme production, as knocking down this transporter mice embryonically lethal accompanied by severe anemia plus oxidative damage. role unknown, but given its...
Abstract ATP-binding cassette (ABC) exporters transport substrates across biological membranes using ATP hydrolysis by a process that involves switching between inward- and outward-facing conformations. Most of the structural studies ABC proteins have been performed with in detergent micelles, locked specific conformations and/or at low temperature. In this article, we present recent data from our laboratories where studied prototypical exporter MsbA during hydrolysis, 37°C, reconstituted...
Abstract Heme biosynthesis occurs through a series of reactions that take place within the cytoplasm and mitochondria, thus intermediates need to move across these cellular compartments. However, specific membrane transport mechanisms involved in process are not yet identified. The ATP-binding cassette protein ABCB10 is essential for normal heme production, as knocking down this transporter mice embryonically lethal accompanied by severe anemia plus oxidative damage. role unknown, but given...