A5034348338- Methane Hydrates and Related Phenomena
- Seismic Waves and Analysis
- Seismology and Earthquake Studies
- Earthquake Detection and Analysis
- Metal-Catalyzed Oxygenation Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Cardiac Ischemia and Reperfusion
- Ion channel regulation and function
- Microbial metabolism and enzyme function
- Nitric Oxide and Endothelin Effects
- Metal complexes synthesis and properties
- Metabolism and Genetic Disorders
- Folate and B Vitamins Research
- Click Chemistry and Applications
- RNA and protein synthesis mechanisms
- Vanadium and Halogenation Chemistry
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- RNA modifications and cancer
- Enzyme Structure and Function
- Heme Oxygenase-1 and Carbon Monoxide
- Acute Kidney Injury Research
- Nuclear and radioactivity studies
- Ion-surface interactions and analysis
- Lipid Membrane Structure and Behavior
- Nuclear reactor physics and engineering
Oregon Health & Science University
2018-2025
Oregon Medical Research Center
2024
Case Western Reserve University
2023
Portland State University
2017-2018
Oregon State University
2011-2016
Abstract ATP-sensitive potassium (K ATP ) channels, composed of four pore-lining Kir6.2 subunits and regulatory sulfonylurea receptor 1 (SUR1) subunits, control insulin secretion in pancreatic β-cells. K channel opening is stimulated by PIP 2 inhibited ATP. Mutations that increase reduce inhibition cause neonatal diabetes. Although considerable evidence has implicated a role for function, previously solved open-channel structures have lacked bound , mechanisms which regulates channels remain...
Significance Vascular K ATP channels formed by the potassium channel Kir6.1 and its regulatory protein SUR2B maintain blood pressure in physiological range. Overactivity of due to genetic mutations either or causes severe cardiovascular pathologies known as Cantú syndrome. The cryogenic electron microscopy structures vascular reported here show multiple, dynamically related conformations subunit SUR2B. Molecular dynamics simulations reveal negatively charged ED-domain SUR2B, a stretch 15...
The planarity of peptide bonds is an assumption that underlies decades theoretical modeling proteins. Peptide strongly deviating from are considered very rare features protein structure occur for functional reasons. Here, empirical analyses atomic-resolution structures reveal trans groups can vary by more than 25° and the true extent nonplanarity underestimated even in 1.2 Å resolution structures. Analyses as a function φ , ψ -backbone dihedral angles show expected value deviates ± 8° planar...
Genetic code expansion has provided the ability to site-specifically incorporate a multitude of noncanonical amino acids (ncAAs) into proteins for wide variety applications, but low ncAA incorporation efficiency can hamper utility this powerful technology. When investigating containing post-translational modification 3-nitro-tyrosine (nitroTyr), we developed second-generation amino-acyl tRNA synthetases (RS) that nitroTyr at efficiencies roughly an order magnitude greater than those...
Pancreatic K ATP channel trafficking defects underlie congenital hyperinsulinism (CHI) cases unresponsive to the opener diazoxide, mainstay medical therapy for CHI. Current clinically used inhibitors have been shown act as pharmacochaperones and restore surface expression of mutants; however, their therapeutic utility impaired CHI is hindered by high-affinity binding, which limits functional recovery rescued channels. Recent structural studies channels employing cryo-electron microscopy...
Pancreatic K ATP channel trafficking defects underlie congenital hyperinsulinism (CHI) cases unresponsive to the opener diazoxide, mainstay medical therapy for CHI. Current clinically used inhibitors have been shown act as pharmacochaperones and restore surface expression of mutants; however, their therapeutic utility trafficking-impaired CHI is hindered by high affinity binding, which limits functional recovery rescued channels. Recent structural studies channels employing cryo-electron...
We report the selection and characterization of an improved acridon-2-ylalanine aminoacyl tRNA synthetase.
Abstract In some bacteria, cysteine is converted to sulfinic acid by dioxygenases (CDO) that are only ∼15–30% identical in sequence mammalian CDOs. Among bacterial proteins having this range of similarity CDO conserve an active site Arg residue (“Arg‐type” enzymes) and a Gln substituted for (“Gln‐type” enzymes). Here, we describe structure from each these enzyme types analyzing structures originally solved structural genomics groups but not published: Bacillus subtilis “Arg‐type” has...
The Escherichia coli sulfur starvation utilization (ssu) operon includes a two-component monooxygenase system consisting of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase, SsuE, and monooxygenase, SsuD. SsuE is part the flavodoxin-like superfamily, we report here crystal structures its apo, FMN-bound, FMNH2-bound forms at ∼2 Å resolution. In crystals, tetramer that dimer dimers similar to those seen for homologous FMN reductases, quinone...
ATP-sensitive potassium (K
Introduction & Objectives: Pancreatic KATP channel trafficking defects underlie congenital hyperinsulinism (CHI) cases unresponsive to the opener diazoxide, mainstay medical therapy for CHI. Current clinically used inhibitors have been shown act as pharmacochaperones (PCs) and restore surface expression of mutants; however, their therapeutic utility CHI is hindered by irreversible binding, which limits functional recovery rescued channels. Cryo-electron microscopy (Cryo-EM) structures...
Pancreatic KATP channel trafficking defects underlie congenital hyperinsulinism (CHI) cases unresponsive to the opener diazoxide, mainstay medical therapy for CHI. Current clinically used inhibitors have been shown act as pharmacochaperones and restore surface expression of mutants; however, their therapeutic utility impaired CHI is hindered by high-affinity binding, which limits functional recovery rescued channels. Recent structural studies channels employing cryo-electron microscopy...