Molecular Determinants of Drug Binding and Selectivity at Muscarinic Acetylcholine Receptors

Grant number: 1138448 | Funding period: 2018 - 2021

Completed

Abstract

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in the human genome, and drugs targeting these receptors account for 30% of marketed drugs. This project aims to determine high resolution structural information on how drugs bind and specifically interact with GPCRs, which will enable future development of selective and effective drugs.

Related publications (5)

Scholarly works icon

Molecular basis of ligand binding and receptor activation at the human A3 adenosine receptor

L Zhang, JI Mobbs, FM Bennetts, H Venugopal, ATN Nguyen, A Christopoulos, D van der Es, LH Heitman, LT May, A Glukhova, DM Thal

2025-12-01

Adenosine receptors (ARs: A<inf>1</inf>AR, A<inf>2A</inf>AR, A<inf>2B</inf>AR, and A<inf>3</inf>AR) are crucial therapeutic target..

Scholarly works icon

Positive allosteric modulation of a GPCR ternary complex

WAC Burger, CJ Draper-Joyce, C Valant, A Christopoulos, DM Thal

2024-09-13

The activation of a G protein–coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G..

Scholarly works icon

Xanomeline displays concomitant orthosteric and allosteric binding modes at the M4 mAChR

WAC Burger, V Pham, Z Vuckovic, AS Powers, JI Mobbs, Y Laloudakis, A Glukhova, D Wootten, AB Tobin, PM Sexton, SM Paul, CC Felder, R Danev, RO Dror, A Christopoulos, C Valant, DM Thal

2023-12-01

The M<inf>4</inf> muscarinic acetylcholine receptor (M<inf>4</inf> mAChR) has emerged as a drug target of high therapeutic interes..

Scholarly works icon

Cryo-EM structures of human arachidonate 12S-lipoxygenase bound to endogenous and exogenous inhibitors

JI Mobbs, KA Black, M Tran, WAC Burger, H Venugopal, TR Holman, M Holinstat, DM Thal, A Glukhova

2023-10-05

Human 12-lipoxygenase (12-LOX) is a key enzyme involved in platelet activation, and the regulation of its activity has been target..

Scholarly works icon

Pharmacological hallmarks of allostery at the M4 muscarinic receptor elucidated through structure and dynamics

Z Vuckovic, J Wang, V Pham, JI Mobbs, MJ Belousoff, A Bhattarai, WAC Burger, G Thompson, M Yeasmin, V Nawaratne, K Leach, ET van der Westhuizen, E Khajehali, YL Liang, A Glukhova, D Wootten, CW Lindsley, A Tobin, P Sexton, R Danev

2023-05-30

Allosteric modulation of G protein-coupled receptors (GPCRs) is a major paradigm in drug discovery. Despite decades of research, a..

University of Melbourne Researchers