TY  - GEN
N2  - Extracellular 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.
DO  - 10.6083/q811kk38w
DO  - DOI
AB  - Extracellular 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.
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
T1  - Molecular pharmacology of P2X7 receptor ligands visualized by Cryo-EM
DA  - 2022
AU  - Oken, Adam
AU  - Krishnamurthy, Ipsita
AU  - Lisi, Nic
AU  - Godsey, Michael H.
AU  - Mansoor, Steven E.
L1  - https://digitalcollections.ohsu.edu/record/9572/files/Oken-Adam-OHSU-ResearchWeek-2022.pdf
PB  - Oregon Health and Science University
LA  - eng
PY  - 2022
ID  - 9572
L4  - https://digitalcollections.ohsu.edu/record/9572/files/Oken-Adam-OHSU-ResearchWeek-2022.pdf
KW  - Ion Channels
KW  - Receptors, Purinergic
KW  - structural biology
KW  - cryo-em
KW  - p2x7
KW  - p2xrs
TI  - Molecular pharmacology of P2X7 receptor ligands visualized by Cryo-EM
Y1  - 2022
L2  - https://digitalcollections.ohsu.edu/record/9572/files/Oken-Adam-OHSU-ResearchWeek-2022.pdf
LK  - https://digitalcollections.ohsu.edu/record/9572/files/Oken-Adam-OHSU-ResearchWeek-2022.pdf
UR  - https://digitalcollections.ohsu.edu/record/9572/files/Oken-Adam-OHSU-ResearchWeek-2022.pdf
ER  -