Intragenic complementation has been observed at the argininosuccinate lyase (ASL) locus. Intragenic complementation is a phenomenon that occurs when a multimeric protein is formed from subunits produced by different mutant alleles of a gene. The resulting hybrid protein exhibits enzymatic activity that is greater than that found in the oligomeric proteins produced by each mutant allele alone. T...

The nicotinic acetylcholine receptors (nAChRs) are a family of closely related but pharmacologically distinct neurotransmitter-gated ion channels. They are therapeutic targets for a wide range of neurological disorders, and a key issue in drug development is selective targeting among the more than 20 subtypes of nAChRs that are known. The present work evaluates a proposed hydrogen bonding inter...

C ombination therapy that includes inhibitors of HIV-1 protease (HIVp) are necessary to treat HIV-infected patients. Currently, there are eight peptidic and two nonpeptidic drugs on the market that competitively bind in the active site and inhibit HIVp by mimicking substrates and the transition state of peptide cleavage. The discovery of novel inhibitors is still a very active area of research ...

BACKGROUND The purpose of this study was to determine how the activation of different regulatory domains of the NMDA complex affects the antianxiety effect of antagonists acting at its distinct binding sites. METHODS The anxiolytic-like activity was assessed by the elevated plus-maze test in mice. RESULTS The anxiolytic activity of CGP 37849 (a competitive NMDA receptor antagonist) and L-70...

Berger, Albert J., Stéphane Dieudonné, and Philippe Ascher. heteromeric NMDA-Rs expressed in Xenopus oocytes and Glycine uptake governs glycine site occupancy at NMDA receptors can reach a few micromolar for other expressed heteromeric of excitatory synapses. J. Neurophysiol. 80: 3336–3340, 1998. At NMDA-Rs (Johnson and Ascher 1992; Mayer et al. 1989; central synapses occupation of glycine bind...

The N-methyl-D-aspartate (NMDA) receptor complex in brain is a glutamate receptor subtype with several recognition sites including a glycine site that is able to modulate and activate allosterically the receptor. This receptor may be important in the regulation of developmental synaptic plasticity. The release of glutamate and consequent overstimulation of NMDA receptors that follows hypoxia-is...

In the central nervous system, activation of N-methyl-D-aspartate receptor (NMDA-R) glycine binding sites is a prerequisite for activation of postsynaptic NMDA-Rs by the excitatory neurotransmitter glutamate. Here we provide electrophysiological evidence that the glycine binding sites of presynaptic NMDA-Rs regulate glutamate release in layer II/III pyramidal neurons of the rat visual cortex. S...

Glycine conjugation, a phase II detoxification process, is catalyzed by glycine N-acyltransferase (GLYAT; E.C. 2.3.1.13). GLYAT detoxifies various xenobiotics, such as benzoic acid, and endogenous organic acids, such as isovaleric acid, which makes GLYAT important in the management of organic acidemias in humans. We cloned the open reading frame encoding the bovine ortholog of GLYAT from bovine...

5-Aminolevulinate synthase (ALAS) is the first enzyme of the heme biosynthetic pathway in non-plant eukaryotes and the alpha-subclass of purple bacteria. The pyridoxal 5'-phosphate cofactor at the active site undergoes changes in absorptive properties during substrate binding and catalysis that have allowed us to study the kinetics of these reactions spectroscopically. Rapid scanning stopped-fl...