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Episode 85 of the Dr. GPCR podcast is here! 🎧Hear Dr. Watch the full video with a paid Dr.

November 2021 Dr. Kevin Pfleger and Dr. "Congratulations to Perkins Professor Kevin Pfleger and Dr Elizabeth Johnstone who were awarded one of

🎙️ Episode 87 of the @DrGPCR podcast with Dr. Bianca Plouffe is available!

📢 Did you know that this 3rd Edition of the Dr.

the kinetic factors that enhance in vivo efficacy beyond traditional potency metrics, as presented by Dr Dr. That's exactly what Dr. Dr. Submit your paper today to secure your work in Volume II ➤ Why Dr.

☕ We are excited to announce our rescheduled Dr. GPCR Virtual Cafe session with Dr.

🌟The Dr. GPCR event of the year is the 3rd edition of the Summit. Become a Dr. GPCR Ecosystem site member to attend the Summit, it’s free!

⚠️Mark your calendar for the Dr. GPCR Summit 2022 held between Oct. 10 - 16, it's FREE!

. 🔍 This Week in Dr. This week, Dr. Featured Talk: Dr. Terry Kenakin on The Kinetics of Allostery . Secure your seat today ➤ Why Dr. Read the Premium edition here ➤ What our members say 🗣️ "Dr.

📅 Our FREE Dr. GPCR Summit 2022 is less than a month away!

forward Meet both the global biotech community and Boston’s local innovators in one room Be part of Dr Be Part of the GPCR Community Dr.

Join Dr. Here’s who we've talked to so far: 🎥 Check out the interview with Dr. . 🌐 Why Dr. GPCR Is in This Conversation At Dr.   📚 Terry’s Corner — The Only On-Demand Pharmacology Hub with Dr. Kenakin Himself If you’re part of the Dr.

July 2022 "I’m happy to share that I’m starting a new position as Scientific co-founder LASEREDD Therapeutics" Ross Bathgate Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipids have been shown to stabilize an active conformation of class A G-protein coupled receptors (GPCRs) through a conserved binding site, not present in class B GPCRs. For class B GPCRs, previous molecular dynamics (MD) simulation studies have shown PI(4,5)P2 interacting with the Glucagon receptor (GCGR), which constitutes an important target for diabetes and obesity therapeutics. In this work, we applied MD simulations supported by native mass spectrometry (nMS) to study lipid interactions with GCGR. We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR. Specifically, we find the PI(4,5)P2 lipids to have a higher affinity toward the inactive conformation of GCGR. Interestingly, we find that in contrast to class A GPCRs, PI(4,5)P2 appear to stabilize the inactive conformation of GCGR through a binding site conserved across class B GPCRs but absent in class A GPCRs. This suggests differences in the regulatory function of PI(4,5)P2 between class A and class B GPCRs." Read more at the source #DrGPCR #GPCR #IndustryNews

A Broader Lens: Dr. GPCR As the co-founder of Dr.

September 2022 "In the Wnt-β-catenin pathway, Wnt binding to Frizzled (Fzd) and LRP5 or LRP6 (LRP5/6) co-receptors inhibits the degradation of the transcriptional coactivator β-catenin by recruiting the cytosolic effector Dishevelled (Dvl). Polymerization of Dvl at the plasma membrane recruits the β-catenin destruction complex, enabling the phosphorylation of LRP5/6, a key step in inhibiting β-catenin degradation. Using purified Fzd proteins reconstituted in lipid nanodiscs, we investigated the factors that promote the recruitment of Dvl to the plasma membrane. We found that the affinity of Fzd for Dvl was not affected by Wnt ligands, in contrast to other members of the GPCR superfamily for which the binding of extracellular ligands affects the affinity for downstream transducers. Instead, Fzd-Dvl binding was enhanced by increased concentration of the lipid PI(4,5)P2, which is generated by Dvl-associated lipid kinases in response to Wnt and which is required for LRP5/6 phosphorylation. Moreover, binding to Fzd did not promote Dvl DEP domain dimerization, which has been proposed to be required for signaling downstream of Fzd. Our findings suggest a positive feedback loop in which Wnt-stimulated local PI(4,5)P2 production enhances Dvl recruitment and further PI(4,5)P2 production to support Dvl polymerization, LRP5/6 phosphorylation, and β-catenin stabilization." Read more at the source #DrGPCR #GPCR #IndustryNews

Tomorrow is the day for another Dr. GPCR Virtual Cafe. This time with none other than Dr. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

June 2022 "We’re delighted to welcome Dr Ed Brennan as our new Vice President, Head of Clinical Development Dr Brennan has extensive experience across all phases of clinical development, and across multiple therapeutic

Dr. Register and join your colleagues in September ➤ Why Dr. GPCR Premium Membership Gives You an Edge In a world filled with noise, Dr. ” - DrGPCR University Course Attendee Get a competitive advantage—Join Dr.

November 2021 Read more at the source #DrGPCR #GPCR #IndustryNews

Excited to hear Dr. Register here (FREE) https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe #drgpcr #gpcr #virtualcafe

Excited to hear Dr. automated micro-plate-based methods for quantifying #GPCR activation. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe

Come attend this month's virtual café talk to see the awesome work of Dr. Register here (FREE) https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

Join us and learn how to quantify your kinetic GPCR signaling from the expert himself: Dr. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

Be sure to signup for the next Virtual Cafe of Dr. GPCR on the 24th of June! This time, the GPCRdb team ( Dr. David Gloriam , Dr. Reserve your spot for free at: https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #GPCR #GPCRs #DrGPCR

Join us for a fantastic introduction to GPCRdb with Dr. David Gloriam and Dr. Albert Kooistra. Register today: https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

April 2022 Read more at the source #DrGPCR #GPCR #IndustryNews

Did you register for our next Dr. GPCR Virtual Cafe? Register today! Addgene's Dr. research or you want to share your materials, this is the place to go. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe

Join us for the first virtual cafe talk to hear about the amazing work that Dr. Brian Arey is doing. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

September 2022 "Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid receptor (MOR), whereas naloxone, with only slight structural changes compared to morphine, exhibits inhibitory effect, and is used to treat opioid abuse. The mechanism by which the MOR distinguishes between the two is unclear. Molecular dynamics (MD) simulations on a 1-μs time scale and metadynamics-enhanced conformational sampling are used here to determine the different interactions of these two ligands with MOR: morphine adjusted its pose by continuously flipping deeper into the pocket, whereas naloxone failed to penetrate deeper because its allyl group conflicts with several residues of MOR. The endogenous peptide ligand endomorphin-1 (EM-1) underwent almost no significant conformational changes during the MD simulations. To validate these processes, we employed GIRK4S143T, a MOR-activated Gβγ-protein effector, in combination with mutagenesis and electrophysiological recordings. We verified the role of some key residues in the dynamic recognition of naloxone and morphine and identified the key residue I322, which leads to differential recognition of morphine and naloxone while assisting EM-1 in activating MOR. Reducing the side chain size of I322 (MORI322A) transformed naloxone from an inhibitor directly into an agonist of MOR, and I322A also significantly attenuated the potency of MOR on EM-1, confirming that binding deep in the pocket is critical for the agonistic effect of MOR. This finding reveals a dynamic mechanism for the response of MOR to different ligands and provides a basis for the discovery of new ligands for MOR at the atomic level." Read more at the source #DrGPCR #GPCR #IndustryNews