Paper Citing NAMD - Abstract
Grimes, Leanne; Young, Mark T.
Purinergic P2X Receptors: Structural and Functional Features Depicted by X-Ray and Molecular Modelling Studies
CURRENT MEDICINAL CHEMISTRY, 22:783-798, 2015
The publication of the first crystal structures of the zebrafish P2X4 receptor in 2009 was a pivotal moment; for the first time, researchers were able to interpret their experimental data in a structural context. Several research groups immediately set about using the data to make molecular models of the better-understood mammalian P2X receptors, in order to design and interpret the results of new, more focused structure- function experiments. In 2012, the publication of the crystal structure of zebrafish P2X4 in the ATP-bound state gave further insights into the mechanism of ligand binding and its coupling to ion channel activation, initiating a new cycle of modelling, experimentation and interpretation. The purpose of this review is to describe our current understanding of the 3D- structure of P2X receptors, by highlighting the strengths and limitations of the zebrafish P2X4 crystal structures, discussing how the molecular models derived from them have been made, and what they have been used for, and explaining why crystal structures of mammalian P2X receptors are still needed to uncover the molecular mechanisms of differential agonist/antagonist potency, allosteric modulation, pore dilatation and desensitisation.
