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Thyrotropin-releasing hormone (TRH) receptor (TRH-R) complementary DNAs have been cloned from several species. The deduced amino acid sequences are compatible with TRH-R being a seven-transmembrane-spanning G protein-coupled receptor. These complementary DNAs and reagents derived from them have permitted detailed study of TRH-R biology at the molecular and(More)
The detection of sweet-tasting compounds is mediated in large part by a heterodimeric receptor comprised of T1R2+T1R3. Lactisole, a broad-acting sweet antagonist, suppresses the sweet taste of sugars, protein sweeteners, and artificial sweeteners. Lactisole's inhibitory effect is specific to humans and other primates; lactisole does not affect responses to(More)
Desensitization of the contractile response mediated by the 5-hydroxytryptamine2 (5-HT2) receptor in the isolated guinea-pig trachea and rabbit aorta is a time-dependent process and therefore it has been characterized by an apparent rate constant obtained from a kinetic analysis. Under similar conditions, desensitization of the response in the trachea is(More)
Acetylcholinesterases (AChEs) are characterized by a high net negative charge and by an uneven surface charge distribution, giving rise to a negative electrostatic potential extending over most of the molecular surface. To evaluate the contribution of these electrostatic properties to the catalytic efficiency, 20 single- and multiple-site mutants of human(More)
The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. This discovery has increased our understanding at the molecular level of the mechanisms underlying sweet taste. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric(More)
It is well recognized that base sequence exerts a significant influence on the properties of DNA and plays a significant role in protein-DNA interactions vital for cellular processes. Understanding and predicting base sequence effects requires an extensive structural and dynamic dataset which is currently unavailable from experiment. A consortium of(More)
The artificial sweetener cyclamate tastes sweet to humans, but not to mice. When expressed in vitro, the human sweet receptor (a heterodimer of two taste receptor subunits: hT1R2 + hT1R3) responds to cyclamate, but the mouse receptor (mT1R2 + mT1R3) does not. Using mixed-species pairings of human and mouse sweet receptor subunits, we determined that(More)
Definition of the unfolded state of proteins is essential for understanding their stability and folding on biological timescales. Here, we find that under near physiological conditions the configurational ensemble of the unfolded state of the simplest protein structure, polyalanine alpha-helix, cannot be described by the commonly used Flory random coil(More)
SCF (Skp1 x CUL1 x F-box protein x ROC1) E3 ubiquitin ligase and Cdc34 E2-conjugating enzyme catalyze polyubiquitination in a precisely regulated fashion. Here, we describe biochemical evidence suggesting an autoinhibitory role played by the human CUL1 ECTD (extreme C-terminal domain; spanning the C-terminal 50 amino acids), a region that is predicted to(More)
Phosphoinositides like phosphatidylinositol 4,5-bisphosphate (PIP(2)) are negatively charged lipids that play a pivotal role in membrane trafficking, signal transduction, and protein anchoring. We have designed a force field for the PIP(2) headgroup using quantum mechanical methods and characterized its properties inside a lipid bilayer using molecular(More)