Allosteric Modulator Binding Sites Research Articles

The binding site for allosteric modulators of AMPA receptor

The binding site for allosteric modulators of AMPA receptor

The binding site of aminergic G protein-coupled receptors: the transmembrane segments and second extracellular loop.

In the current chapter, we review approaches to the identification of the residues forming the binding sites for agonists, antagonists, and allosteric modulators in the family of aminergic G protein-coupled receptors (GPCRs). We then review the structural bases for ligand binding and pharmacological specificity based on the application of these methods to muscarinic cholinergic, adrenergic, dopaminergic, serotonergic, and histaminergic receptors, using the high resolution rhodopsin structure as a template. Furthermore, we propose a critical role of the second extracellular loop in forming the binding site for small molecular weight aminergic ligands, much as this loop dives down into the binding-site crevice and contacts retinal in rhodopsin.

Cloning of a Complete Protein-Coding Sequence of Human Platelet-Type Phosphofructokinase Isozyme from Pancreatic Islet

We have cloned a full length protein-coding sequence of human platelet-type phosphofructokinase (PFK) from pancreatic islet cDNA library. The platelet-type PFK was composed of 784 amino acids and had a deduced molecular weight of 85590. Homologies in the primary structure with muscle- and liver-type PFK were 71 and 67%. Clear similarities of the amino and carboxyl halves with a prokaryotic PFK indicated an evolutionary event that duplicated genes of a prototype PFK fused into larger genes of eukaryotic PFKs. Amino acid residues constituting the binding sites for various allosteric modulators were well conserved, while a couple of different residues at the inhibitory ATP sites among three isozymes may partly explain their varied degree of sensitivities to ATP. Considerable amount of platelet-type PFK expression was demonstrated in brain, heart, kidney, colon and testis