Path to the Desensitized State of Ligand-Gated Ion Channels: Why Are Inhibitory and Excitatory Receptors Different?
The family of pentameric ligand-gated ion channels (pLGICs) includes both inhibitory and excitatory receptors. Electrophysiological methods have explored the time-dependent ion currents induced by their neurotransmitter agonists. Kinetic modeling requires a minimum of three conformational states: resting, active, and desensitized. However, current traces of inhibitory and excitatory pLGICs differ substantially. Reproducing their basic features requires different state connectivity: whether the desensitized state is accessed from the resting or active state. It is surprising that a property as fundamental as state connectivity would differ within the same family. So, we explore the possibility that the connectivity is the same, but corresponding states differ in function: Analogous states on the free energy landscape have similar structure, but differ in ion conductivity, free energies, and agonist binding affinities. This hypothesis is tested using a kinetic model in which agonist and anesthetics modulate...
We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure–activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally dive ... more
Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is ... more
This review focuses on the type A cytochrome c oxidases (CcO), which are found in all mitochondria and also in several aerobic bacteria. CcO catalyzes the respiratory reduction of dioxygen (O2) to water by an intriguing mechanism, the details of which are fairly well understood today as a r ... more
Rohm and Haas Powder Coatings is delighted to announce that its Reading, Pennsylvania, facility is the first site in the world to receive the RCMS® Site Certification awarded by the American Chemical Council (ACC).
When Raj Gupta, Chairman and CEO of Rohm and Haas Company, became Chairman ... more