Literature DB >> 24212135

Dynamic ligand binding dictates partial agonism at a G protein-coupled receptor.

Andreas Bock1, Brian Chirinda2, Fabian Krebs2, Regina Messerer3, Julia Bätz4, Mathias Muth3, Clelia Dallanoce5, Dominika Klingenthal2, Christian Tränkle2, Carsten Hoffmann4, Marco De Amici5, Ulrike Holzgrabe3, Evi Kostenis6, Klaus Mohr2.   

Abstract

We present a new concept of partial agonism at G protein-coupled receptors. We demonstrate the coexistence of two functionally distinct populations of the muscarinic M2 receptor stabilized by one dynamic ligand, which binds in two opposite orientations. The ratio of orientations determines the cellular response. Our concept allows predicting and virtually titrating ligand efficacy, which opens unprecedented opportunities for the design of drugs with graded activation of the biological system.

Entities:  

Mesh：

Substances：

Year:  2013        PMID： 24212135     DOI： 10.1038/nchembio.1384

Source DB:  PubMed          Journal:  Nat Chem Biol        ISSN： 1552-4450            Impact factor:   15.040


  30 in total

1.  Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M.

Authors:  C Dallanoce; P Conti; M De Amici; C De Micheli; E Barocelli; M Chiavarini; V Ballabeni; S Bertoni; M Impicciatore
Journal:  Bioorg Med Chem       Date:  1999-08       Impact factor: 3.641

2.  Design, synthesis, and action of oxotremorine-related hybrid-type allosteric modulators of muscarinic acetylcholine receptors.

Authors:  Teresa Disingrini; Mathias Muth; Clelia Dallanoce; Elisabetta Barocelli; Simona Bertoni; Kerstin Kellershohn; Klaus Mohr; Marco De Amici; Ulrike Holzgrabe
Journal:  J Med Chem       Date:  2006-01-12       Impact factor: 7.446

3.  A FlAsH-based FRET approach to determine G protein-coupled receptor activation in living cells.

Authors:  Carsten Hoffmann; Guido Gaietta; Moritz Bünemann; Stephen R Adams; Silke Oberdorff-Maass; Björn Behr; Jean-Pierre Vilardaga; Roger Y Tsien; Mark H Ellisman; Martin J Lohse
Journal:  Nat Methods       Date:  2005-02-17       Impact factor: 28.547

Review 4.  How many drug targets are there?

Authors:  John P Overington; Bissan Al-Lazikani; Andrew L Hopkins
Journal:  Nat Rev Drug Discov       Date:  2006-12       Impact factor: 84.694

Review 5.  Allosteric modulation of G protein-coupled receptors.

Authors:  Lauren T May; Katie Leach; Patrick M Sexton; Arthur Christopoulos
Journal:  Annu Rev Pharmacol Toxicol       Date:  2007       Impact factor: 13.820

6.  The dynamic process of β(2)-adrenergic receptor activation.

Authors:  Rie Nygaard; Yaozhong Zou; Ron O Dror; Thomas J Mildorf; Daniel H Arlow; Aashish Manglik; Albert C Pan; Corey W Liu; Juan José Fung; Michael P Bokoch; Foon Sun Thian; Tong Sun Kobilka; David E Shaw; Luciano Mueller; R Scott Prosser; Brian K Kobilka
Journal:  Cell       Date:  2013-01-31       Impact factor: 41.582

Review 7.  The structure and function of G-protein-coupled receptors.

Authors:  Daniel M Rosenbaum; Søren G F Rasmussen; Brian K Kobilka
Journal:  Nature       Date:  2009-05-21       Impact factor: 49.962

8.  Dualsteric GPCR targeting: a novel route to binding and signaling pathway selectivity.

Authors:  Johannes Antony; Kerstin Kellershohn; Marion Mohr-Andrä; Anna Kebig; Stefanie Prilla; Mathias Muth; Eberhard Heller; Teresa Disingrini; Clelia Dallanoce; Simona Bertoni; Jasmin Schrobang; Christian Tränkle; Evi Kostenis; Arthur Christopoulos; Hans-Dieter Höltje; Elisabetta Barocelli; Marco De Amici; Ulrike Holzgrabe; Klaus Mohr
Journal:  FASEB J       Date:  2008-10-08       Impact factor: 5.191

Review 9.  Molecular signatures of G-protein-coupled receptors.

Authors:  A J Venkatakrishnan; Xavier Deupi; Guillaume Lebon; Christopher G Tate; Gebhard F Schertler; M Madan Babu
Journal:  Nature       Date:  2013-02-14       Impact factor: 49.962

10.  The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor.

Authors:  Tony Warne; Rouslan Moukhametzianov; Jillian G Baker; Rony Nehmé; Patricia C Edwards; Andrew G W Leslie; Gebhard F X Schertler; Christopher G Tate
Journal:  Nature       Date:  2011-01-13       Impact factor: 49.962
View more
  14 in total

Review 1.  Optical probes based on G protein-coupled receptors - added work or added value?

Authors:  A D Stumpf; C Hoffmann
Journal:  Br J Pharmacol       Date:  2015-12-19       Impact factor: 8.739

Review 2.  Superagonism at G protein-coupled receptors and beyond.

Authors:  R Schrage; A De Min; K Hochheiser; E Kostenis; K Mohr
Journal:  Br J Pharmacol       Date:  2015-10-24       Impact factor: 8.739

3.  Competitive association binding kinetic assays: a new tool to detect two different binding orientations of a ligand to its target protein under distinct conditions?

Authors:  Hans-Joachim Wittmann; Andrea Strasser
Journal:  Naunyn Schmiedebergs Arch Pharmacol       Date:  2017-02-20       Impact factor: 3.000

4.  Ligand Binding Ensembles Determine Graded Agonist Efficacies at a G Protein-coupled Receptor.

Authors:  Andreas Bock; Marcel Bermudez; Fabian Krebs; Carlo Matera; Brian Chirinda; Dominique Sydow; Clelia Dallanoce; Ulrike Holzgrabe; Marco De Amici; Martin J Lohse; Gerhard Wolber; Klaus Mohr
Journal:  J Biol Chem       Date:  2016-06-13       Impact factor: 5.157

5.  Gaussian Accelerated Molecular Dynamics: Theory, Implementation, and Applications.

Authors:  Yinglong Miao; J Andrew McCammon
Journal:  Annu Rep Comput Chem       Date:  2017-08-10

Review 6.  GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures.

Authors:  Ichio Shimada; Takumi Ueda; Yutaka Kofuku; Matthew T Eddy; Kurt Wüthrich
Journal:  Nat Rev Drug Discov       Date:  2018-11-09       Impact factor: 84.694

7.  Graded activation and free energy landscapes of a muscarinic G-protein-coupled receptor.

Authors:  Yinglong Miao; J Andrew McCammon
Journal:  Proc Natl Acad Sci U S A       Date:  2016-10-10       Impact factor: 11.205

8.  Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor.

Authors:  Steven D Chang; S Wayne Mascarella; Skylar M Spangler; Vsevolod V Gurevich; Hernan A Navarro; F Ivy Carroll; Michael R Bruchas
Journal:  Mol Pharmacol       Date:  2015-07-01       Impact factor: 4.436

9.  2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts.

Authors:  Amy Hauck Newman; Francisco O Battiti; Alessandro Bonifazi
Journal:  J Med Chem       Date:  2019-09-24       Impact factor: 7.446

10.  The Importance of Ligand-Receptor Conformational Pairs in Stabilization: Spotlight on the N/OFQ G Protein-Coupled Receptor.

Authors:  Rebecca L Miller; Aaron A Thompson; Claudio Trapella; Remo Guerrini; Davide Malfacini; Nilkanth Patel; Gye Won Han; Vadim Cherezov; Girolamo Caló; Vsevolod Katritch; Raymond C Stevens
Journal:  Structure       Date:  2015-10-29       Impact factor: 5.006
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.