Nathan Alexander

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We present a model of interaction of Gi protein with the activated receptor (R*) rhodopsin, which pinpoints energetic contributions to activation and reconciles the β2 adrenergic receptor-Gs crystal structure with new and previously published experimental data. In silico analysis demonstrated energetic changes when the Gα C-terminal helix (α5) interacts(More)
Arrestin-1 (visual arrestin) binds to light-activated phosphorylated rhodopsin (P-Rh*) to terminate G-protein signaling. To map conformational changes upon binding to the receptor, pairs of spin labels were introduced in arrestin-1 and double electron-electron resonance was used to monitor interspin distance changes upon P-Rh* binding. The results indicate(More)
Electron density maps of membrane proteins or large macromolecular complexes are frequently only determined at medium resolution between 4 Å and 10 Å, either by cryo-electron microscopy or X-ray crystallography. In these density maps, the general arrangement of secondary structure elements (SSEs) is revealed, whereas their directionality and connectivity(More)
OBJECTIVE To highlight concepts critical to achieving successful repair and avoiding intracranial complications in the treatment of cerebrospinal fluid (CSF) leaks from the lateral recess of the sphenoid sinus (LRS). DESIGN Outcomes study. SETTING Tertiary referral university hospital. PATIENTS Eleven patients with LRS CSF leaks from June 2008 to June(More)
Clustering algorithms are used as data analysis tools in a wide variety of applications in Biology. Clustering has become especially important in protein structure prediction and virtual high throughput screening methods. In protein structure prediction, clustering is used to structure the conformational space of thousands of protein models. In virtual high(More)
An increasingly used parameter in structural biology is the measurement of distances between spin labels bound to a protein. One limitation to these measurements is the unknown position of the spin label relative to the protein backbone. To overcome this drawback, we introduce a rotamer library of the methanethiosulfonate spin label (MTSSL) into the protein(More)
Fluids collecting in surgical wounds in both dogs and man have been shown to lose progressively the ability to opsonize bacteria for phagocytosis and killing of bacteria by normal neutrophils. Since the collection of fluids in potentially contaminated wounds also interferes with access of phagocytic cells to contaminating bacteria and provides a pablum for(More)
OBJECTIVES/HYPOTHESIS Evidence indicates that decreased mucociliary clearance (MCC) is a major contributing feature to chronic rhinosinusitis. Tobacco-smoke exposure is thought to inhibit transepithelial Cl(-) secretion, a major determinant of airway surface liquid hydration and MCC. The objective of the current study was to evaluate the effects of acrolein(More)
Site-directed spin labeling electron paramagnetic resonance (SDSL-EPR) is often used for the structural characterization of proteins that elude other techniques, such as X-ray crystallography and nuclear magnetic resonance (NMR). However, high-resolution structures are difficult to obtain due to uncertainty in the spin label location and sparseness of(More)
As many key proteins evade crystallization and remain too large for nuclear magnetic resonance spectroscopy, electron paramagnetic resonance (EPR) spectroscopy combined with site-directed spin labeling offers an alternative approach for obtaining structural information. Such information must be translated into geometric restraints to be used in computer(More)