In the central nervous system, glycine is a co-agonist with glutamate at the N-methyl-D-aspartate subtype of glutamate receptors and also an agonist at inhibitory, strychnine-sensitive glycine receptors. The GLYT1 subtypes of glycine transporters (GLYTs) are responsible for regulation of glycine at excitatory synapses, whereas a combination of GLYT1 and GLYT2 subtypes of glycine transporters ar...

Results: Protein variants containing glycine and aromatic residues positioned across β strands in both antiparallel and parallel orientations were studied. The pairing of glycine and phenylalanine across antiparallel strands resulted in a synergistic increase in protein stability. Dramatic differences in stability were observed for the parallel β-sheet mutants, which were dependent upon the typ...

Diphtheria toxoid, the principle component of diphtheria vaccines, is prepared by inactivating diphtheria toxin with formaldehyde and glycine. The treatment introduces intramolecular cross-links and intermolecular formaldehyde/glycine adducts in diphtheria toxin. The purpose of the present study was to elucidate the nature and location of formaldehyde-induced modifications at two functional sit...

Six novel inhibitors of Vibrio harveyi chitinase A (VhChiA), a family-18 chitinase homolog, were identified by in vitro screening of a library of pharmacologically active compounds. Unlike the previously identified inhibitors that mimicked the reaction intermediates, crystallographic evidence from 14 VhChiA-inhibitor complexes showed that all of the inhibitor molecules occupied the outer part o...

The maleylpyruvate isomerase NagL from Ralstonia sp. strain U2, which has been structurally characterized previously, catalyzes the isomerization of maleylpyruvate to fumarylpyruvate. It belongs to the class zeta glutathione S-transferases (GSTZs), part of the cytosolic GST family (cGSTs). In this study, site-directed mutagenesis was conducted to probe the functions of 13 putative active site r...

NA-glycine is an endogenous lipid molecule with analgesic properties, which is structurally similar to the endocannabinoids 2-AG and anandamide but does not interact with cannabinoid receptors. NA-glycine has been suggested to act at the G-protein coupled receptors GPR18 and GPR92. Recently, we have described that NA-glycine can also modulate recombinant α1β2γ2 GABAA receptors. Here we characte...

3-Amino-1-hydroxypyrrolid-2-one (HA-966) has been known for several years as an excitatory amino acid antagonist, acting principally at the N-methyl-D-aspartate (NMDA) receptor subtype. We report here that HA-966 blocks NMDA responses through a selective interaction with the glycine modulatory site present within the receptor complex. In radioligand binding experiments, HA-966 inhibited strychn...

NMDA receptor currents desensitize in an agonist-dependent manner when either the glutamate or glycine agonist is subsaturating. This may result from a conformational change in the NMDA receptor protein that lowers glutamate and glycine binding site affinity induced by co-agonist binding, channel opening, or ion permeation. We have used whole-cell voltage clamp of cultured hippocampal neurons w...

NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain. They are tetrameric complexes composed of glycine-binding GluN1 and GluN3 subunits together with glutamate-binding GluN2 subunits. Subunit-selective antagonists that discriminate between the glycine sites of GluN1 and GluN3 subunits would be valuable pharmacological tools for studies on the func...

1. The kinetics of glycine-sensitive, N-methyl-D-aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique. 2. The degree of fast NMDA-receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 nM to 2.5 microM potentiated desensitized NMDA responses (873% +/- 101%) to a greate...