Biomaterial Database

Structural Basis for Allosteric Modulation of Class B G Protein-Coupled Receptors. 2020

Denise Wootten, and Laurence J Miller

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, and Department of Pharmacology, Monash University, Parkville 3052, Australia; email: denise.wootten@monash.edu.

Recent advances in our understanding of the structure and function of class B G protein-coupled receptors (GPCRs) provide multiple opportunities for targeted development of allosteric modulators. Given the pleiotropic signaling patterns emanating from these receptors in response to a variety of natural agonist ligands, modulators have the potential to sculpt the responses to meet distinct needs of different groups of patients. In this review, we provide insights into how this family of GPCRs differs from the rest of the superfamily, how orthosteric agonists bind and activate these receptors, the potential for allosteric modulators to interact with various regions of these targets, and the allosteric influence of endogenous proteins on the pharmacology of these receptors, all of which are important considerations when developing new therapies.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076722	Drug Development	The entire process of bringing a new drug to the market. It includes both preclinical and clinical testing, and regulatory approval.	Computational Prediction of Drug-Target Interactions,Drug Target Prediction,Medication Development,Pharmaceutical Development,Development, Drug,Development, Medication,Development, Pharmaceutical,Drug Target Predictions,Prediction, Drug Target,Target Prediction, Drug
D000494	Allosteric Regulation	The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.	Regulation, Allosteric,Allosteric Regulations,Regulations, Allosteric
D000495	Allosteric Site	A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.	Allosteric Sites,Site, Allosteric,Sites, Allosteric
D043562	Receptors, G-Protein-Coupled	The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.	G Protein Coupled Receptor,G-Protein-Coupled Receptor,G-Protein-Coupled Receptors,G Protein Coupled Receptors,Receptor, G-Protein-Coupled,Receptors, G Protein Coupled