000009572 001__ 9572
000009572 005__ 20240412114550.0
000009572 0247_ $$2DOI$$a10.6083/q811kk38w
000009572 037__ $$aIR
000009572 041__ $$aeng
000009572 245__ $$aMolecular pharmacology of P2X7 receptor ligands visualized by Cryo-EM
000009572 260__ $$bOregon Health and Science University
000009572 269__ $$a2022
000009572 336__ $$aAbstract
000009572 520__ $$aExtracellular ATP is a critical signaling molecule that is found in a wide range of concentrations across cellular environments. The family of nonselective cation channels that recognize extracellular ATP, termed P2X receptors (P2XRs), is composed of seven sub-types (P2X1-P2X7) that assemble as functional homo-trimeric and hetero-trimeric ion channels. The therapeutic potential of P2XRs is an emerging area of research, as overactive P2XRs have been shown to play pathophysiological roles in neuro-inflammation, vascular inflammation, and cell division. Although there are currently no FDA-approved drugs targeting P2XRs, structure-based drug design can provide unique and insightful details into the intricacies of each receptor to facilitate sub-type selective ligands. Here, we highlight potential therapeutically targetable sites in the P2XR family and how single-particle cryogenic electron microscopy (cryo-EM) can be used to advance drug discovery, focusing on two cryo-EM structures; the endogenous agonist ATP bound to P2X7 and the noncompetitive antagonist JNJ-47965567 bound to P2X7.
000009572 540__ $$fCC BY
000009572 542__ $$fIn copyright - joint owners
000009572 650__ $$aIon Channels$$021013
000009572 650__ $$aReceptors, Purinergic$$025217
000009572 6531_ $$astructural biology
000009572 6531_ $$acryo-em
000009572 6531_ $$ap2x7
000009572 6531_ $$ap2xrs
000009572 691__ $$aSchool of Medicine$$041369
000009572 692__ $$aDepartment of Chemical Physiology and Biochemistry$$041400
000009572 7001_ $$aOken, Adam$$uOregon Health and Science University$$041354
000009572 7001_ $$aKrishnamurthy, Ipsita$$uOregon Health and Science University$$041354
000009572 7001_ $$aLisi, Nic$$uOregon Health and Science University$$041354
000009572 7001_ $$aGodsey, Michael H.$$uOregon Health and Science University$$041354
000009572 7001_ $$aMansoor, Steven E.$$uOregon Health and Science University$$041354
000009572 711__ $$aResearch Week$$uOregon Health and Science University$$d2022
000009572 8564_ $$9c1c3700f-2c10-40d1-80d3-c5920e0bc814$$s170652$$uhttps://digitalcollections.ohsu.edu/record/9572/files/Oken-Adam-OHSU-ResearchWeek-2022.pdf
000009572 905__ $$a/rest/prod/q8/11/kk/38/q811kk38w
000009572 980__ $$aResearch Week