Aminergic GPCR–Ligand Interactions: A Chemical and Structural Map of Receptor Mutation DataClick to copy article linkArticle link copied!
- Márton VassMárton VassDivision of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, 1081HZ Amsterdam, The NetherlandsMore by Márton Vass
- Sabina PodlewskaSabina PodlewskaDepartment of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL31-343 Kraków, PolandMore by Sabina Podlewska
- Iwan J. P. de EschIwan J. P. de EschDivision of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, 1081HZ Amsterdam, The NetherlandsMore by Iwan J. P. de Esch
- Andrzej J. BojarskiAndrzej J. BojarskiDepartment of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL31-343 Kraków, PolandMore by Andrzej J. Bojarski
- Rob LeursRob LeursDivision of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, 1081HZ Amsterdam, The NetherlandsMore by Rob Leurs
- Albert J. KooistraAlbert J. KooistraDivision of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, 1081HZ Amsterdam, The NetherlandsDepartment of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, DenmarkMore by Albert J. Kooistra
- Chris de Graaf*Chris de Graaf*E-mail: [email protected]. Phone: +44 (0)1223 949 100.Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, 1081HZ Amsterdam, The NetherlandsSosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge CB21 6DG, U.K.More by Chris de Graaf
Abstract
The aminergic family of G protein-coupled receptors (GPCRs) plays an important role in various diseases and represents a major drug discovery target class. Structure determination of all major aminergic subfamilies has enabled structure-based ligand design for these receptors. Site-directed mutagenesis data provides an invaluable complementary source of information for elucidating the structural determinants of binding of different ligand chemotypes. The current study provides a comparative analysis of 6692 mutation data points on 34 aminergic GPCR subtypes, covering the chemical space of 540 unique ligands from mutagenesis experiments and information from experimentally determined structures of 52 distinct aminergic receptor–ligand complexes. The integrated analysis enables detailed investigation of structural receptor–ligand interactions and assessment of the transferability of combined binding mode and mutation data across ligand chemotypes and receptor subtypes. An overview is provided of the possibilities and limitations of using mutation data to guide the design of novel aminergic receptor ligands.
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(13)
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(3)
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- Ryan P. McGlynn, Meng Cui, Brittany Brems, Otto Holbrook, Raymond G. Booth. Development of 2-Aminotetralin-Type Serotonin 5-HT1 Agonists: Molecular Determinants for Selective Binding and Signaling at 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1F Receptors. ACS Chemical Neuroscience 2024, 15
(2)
, 357-370. https://doi.org/10.1021/acschemneuro.3c00658
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(21)
, 6667-6680. https://doi.org/10.1021/acs.jcim.3c00755
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(15)
, 2727-2742. https://doi.org/10.1021/acschemneuro.3c00267
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(8)
, 2820-2828. https://doi.org/10.1021/acssynbio.2c00205
- Bettina Lengger, Emma E. Hoch-Schneider, Christina N. Jensen, Tadas Jakočiu̅nas, Anja A. Petersen, Thomas M. Frimurer, Emil D. Jensen, Michael K. Jensen. Serotonin G Protein-Coupled Receptor-Based Biosensing Modalities in Yeast. ACS Sensors 2022, 7
(5)
, 1323-1335. https://doi.org/10.1021/acssensors.1c02061
- Lucy Kate Ladefoged, Rebekka Koch, Philip C. Biggin, Birgit Schiøtt. Binding and Activation of Serotonergic G-Protein Coupled Receptors by the Multimodal Antidepressant Vortioxetine. ACS Chemical Neuroscience 2022, 13
(8)
, 1129-1142. https://doi.org/10.1021/acschemneuro.1c00029
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(13)
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(12)
, 8684-8709. https://doi.org/10.1021/acs.jmedchem.1c00692
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(49)
, 31706-31715. https://doi.org/10.1021/acsomega.0c04220
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(9)
, 4579-4602. https://doi.org/10.1021/acs.jmedchem.9b01835
- Holli-Joi Sullivan, Amanda Tursi, Kelly Moore, Alexandra Campbell, Cecilia Floyd, Chun Wu. Binding Interactions of Ergotamine and Dihydroergotamine to 5-Hydroxytryptamine Receptor 1B (5-HT1b) Using Molecular Dynamics Simulations and Dynamic Network Analysis. Journal of Chemical Information and Modeling 2020, 60
(3)
, 1749-1765. https://doi.org/10.1021/acs.jcim.9b01082
- Flavio Ballante, Axel Rudling, Alexey Zeifman, Andreas Luttens, Duy Duc Vo, John J. Irwin, Jan Kihlberg, Jose Brea, Maria Isabel Loza, Jens Carlsson. Docking Finds GPCR Ligands in Dark Chemical Matter. Journal of Medicinal Chemistry 2020, 63
(2)
, 613-620. https://doi.org/10.1021/acs.jmedchem.9b01560
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(19)
, 3295-3310.e8. https://doi.org/10.1016/j.neuron.2024.07.003
- Alejandro Díaz-Holguín, Marcus Saarinen, Duc Duy Vo, Andrea Sturchio, Niclas Branzell, Israel Cabeza de Vaca, Huabin Hu, Núria Mitjavila-Domènech, Annika Lindqvist, Pawel Baranczewski, Mark J. Millan, Yunting Yang, Jens Carlsson, Per Svenningsson. AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine–associated receptor 1. Science Advances 2024, 10
(32)
https://doi.org/10.1126/sciadv.adn1524
- Polina D. Kotova, Ekaterina A. Dymova, Oleg O. Lyamin, Olga A. Rogachevskaja, Stanislav S. Kolesnikov. PI3 kinase inhibitor PI828 uncouples aminergic GPCRs and Ca2+ mobilization irrespectively of its primary target. Biochimica et Biophysica Acta (BBA) - General Subjects 2024, 1868
(8)
, 130649. https://doi.org/10.1016/j.bbagen.2024.130649
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- Jianfang Chen, Yuanpeng Song, Luhan Ma, Yizhou Jin, Jin Yu, Yanzhi Guo, Yan Huang, Xuemei Pu. Computational insights into diverse binding modes of the allosteric modulator and their regulation on dopamine D1 receptor. Computers in Biology and Medicine 2024, 173 , 108283. https://doi.org/10.1016/j.compbiomed.2024.108283
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(13)
, 8615-8640. https://doi.org/10.1039/D3RA07380G
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(1)
https://doi.org/10.1038/s41467-023-39310-x
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(6)
, 571. https://doi.org/10.3390/bios13060571
- Lukas Zell, Alina Bretl, Veronika Temml, Daniela Schuster. Dopamine Receptor Ligand Selectivity—An In Silico/In Vitro Insight. Biomedicines 2023, 11
(5)
, 1468. https://doi.org/10.3390/biomedicines11051468
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(12)
, 103366. https://doi.org/10.1016/j.drudis.2022.103366
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(1)
https://doi.org/10.1038/s41467-021-27911-3
- Xueqian Peng, Linlin Yang, Zixuan Liu, Siyi Lou, Shiliu Mei, Meiling Li, Zhong Chen, Haitao Zhang. Structural basis for recognition of antihistamine drug by human histamine receptor. Nature Communications 2022, 13
(1)
https://doi.org/10.1038/s41467-022-33880-y
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(1)
https://doi.org/10.1038/s41598-022-06591-z
- Morgan Thomas, Noel M. O’Boyle, Andreas Bender, Chris de Graaf. Augmented Hill-Climb increases reinforcement learning efficiency for language-based de novo molecule generation. Journal of Cheminformatics 2022, 14
(1)
https://doi.org/10.1186/s13321-022-00646-z
- Youwen Zhuang, Yue Wang, Bingqing He, Xinheng He, X. Edward Zhou, Shimeng Guo, Qidi Rao, Jiaqi Yang, Jinyu Liu, Qingtong Zhou, Xiaoxi Wang, Mingliang Liu, Weiyi Liu, Xiangrui Jiang, Dehua Yang, Hualiang Jiang, Jingshan Shen, Karsten Melcher, Hong Chen, Yi Jiang, Xi Cheng, Ming-Wei Wang, Xin Xie, H. Eric Xu. Molecular recognition of morphine and fentanyl by the human μ-opioid receptor. Cell 2022, 185
(23)
, 4361-4375.e19. https://doi.org/10.1016/j.cell.2022.09.041
- Berkay Selçuk, Ismail Erol, Serdar Durdağı, Ogün Adebali. Evolutionary association of receptor-wide amino acids with G protein–coupling selectivity in aminergic GPCRs. Life Science Alliance 2022, 5
(10)
, e202201439. https://doi.org/10.26508/lsa.202201439
- Sijie Huang, Peiyu Xu, Dan-Dan Shen, Icaro A. Simon, Chunyou Mao, Yangxia Tan, Huibing Zhang, Kasper Harpsøe, Huadong Li, Yumu Zhang, Chongzhao You, Xuekui Yu, Yi Jiang, Yan Zhang, David E. Gloriam, H. Eric Xu. GPCRs steer Gi and Gs selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors. Molecular Cell 2022, 82
(14)
, 2681-2695.e6. https://doi.org/10.1016/j.molcel.2022.05.031
- Austen B. Casey, Meng Cui, Raymond G. Booth, Clinton E. Canal. “Selective” serotonin 5-HT2A receptor antagonists. Biochemical Pharmacology 2022, 200 , 115028. https://doi.org/10.1016/j.bcp.2022.115028
- Austen B. Casey, Munmun Mukherjee, Ryan P. McGlynn, Meng Cui, Stephen J. Kohut, Raymond G. Booth. A new class of 5‐HT
2A
/5‐HT
2C
receptor inverse agonists: Synthesis, molecular modeling,
in vitro
and
in vivo
pharmacology of novel 2‐aminotetralins. British Journal of Pharmacology 2022, 179
(11)
, 2610-2630. https://doi.org/10.1111/bph.15756
- Riya Khetan, Cintya Dharmayanti, Todd A. Gillam, Eric Kübler, Manuela Klingler-Hoffmann, Carmela Ricciardelli, Martin K. Oehler, Anton Blencowe, Sanjay Garg, Hugo Albrecht. Using GPCRs as Molecular Beacons to Target Ovarian Cancer with Nanomedicines. Cancers 2022, 14
(10)
, 2362. https://doi.org/10.3390/cancers14102362
- Ee Von Moo, Kasper Harpsøe, Alexander S. Hauser, Ikuo Masuho, Hans Bräuner-Osborne, David E. Gloriam, Kirill A. Martemyanov. Ligand-directed bias of G protein signaling at the dopamine D2 receptor. Cell Chemical Biology 2022, 29
(2)
, 226-238.e4. https://doi.org/10.1016/j.chembiol.2021.07.004
- Zhangcheng Chen, Luyu Fan, Huan Wang, Jing Yu, Dengyu Lu, Jianzhong Qi, Fen Nie, Zhipu Luo, Zhen Liu, Jianjun Cheng, Sheng Wang. Structure-based design of a novel third-generation antipsychotic drug lead with potential antidepressant properties. Nature Neuroscience 2022, 25
(1)
, 39-49. https://doi.org/10.1038/s41593-021-00971-w
- Liang Jia, Shengju Li, Wenxuan Dai, Lingna Guo, Zhengrong Xu, Anne M. Scott, Zhe Zhang, Jianfeng Ren, Qinghua Zhang, Thomas S. Dexheimer, Yu-Wen Chung-Davidson, Richard R. Neubig, Qian Li, Weiming Li. Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site. Journal of Biological Chemistry 2021, 297
(5)
, 101268. https://doi.org/10.1016/j.jbc.2021.101268
- Alastair J.H. Brown, Sophie J. Bradley, Fiona H. Marshall, Giles A. Brown, Kirstie A. Bennett, Jason Brown, Julie E. Cansfield, David M. Cross, Chris de Graaf, Brian D. Hudson, Louis Dwomoh, João M. Dias, James C. Errey, Edward Hurrell, Jan Liptrot, Giulio Mattedi, Colin Molloy, Pradeep J. Nathan, Krzysztof Okrasa, Greg Osborne, Jayesh C. Patel, Mark Pickworth, Nathan Robertson, Shahram Shahabi, Christoffer Bundgaard, Keith Phillips, Lisa M. Broad, Anushka V. Goonawardena, Stephen R. Morairty, Michael Browning, Francesca Perini, Gerard R. Dawson, John F.W. Deakin, Robert T. Smith, Patrick M. Sexton, Julie Warneck, Mary Vinson, Tim Tasker, Benjamin G. Tehan, Barry Teobald, Arthur Christopoulos, Christopher J. Langmead, Ali Jazayeri, Robert M. Cooke, Prakash Rucktooa, Miles S. Congreve, Malcolm Weir, Andrew B. Tobin. From structure to clinic: Design of a muscarinic M1 receptor agonist with the potential to treat Alzheimer’s disease. Cell 2021, 184
(24)
, 5886-5901.e22. https://doi.org/10.1016/j.cell.2021.11.001
- Wojciech Pietruś, Rafał Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Jürgen Bajorath. Data-Driven Analysis of Fluorination of Ligands of Aminergic G Protein Coupled Receptors. Biomolecules 2021, 11
(11)
, 1647. https://doi.org/10.3390/biom11111647
- Stefanie Kampen, Duc Duy Vo, Xiaoqun Zhang, Nicolas Panel, Yunting Yang, Mariama Jaiteh, Pierre Matricon, Per Svenningsson, Jose Brea, Maria Isabel Loza, Jan Kihlberg, Jens Carlsson. Structure‐Guided Design of G‐Protein‐Coupled Receptor Polypharmacology. Angewandte Chemie 2021, 133
(33)
, 18170-18178. https://doi.org/10.1002/ange.202101478
- Stefanie Kampen, Duc Duy Vo, Xiaoqun Zhang, Nicolas Panel, Yunting Yang, Mariama Jaiteh, Pierre Matricon, Per Svenningsson, Jose Brea, Maria Isabel Loza, Jan Kihlberg, Jens Carlsson. Structure‐Guided Design of G‐Protein‐Coupled Receptor Polypharmacology. Angewandte Chemie International Edition 2021, 60
(33)
, 18022-18030. https://doi.org/10.1002/anie.202101478
- Attila Egyed, Ádám A. Kelemen, Márton Vass, András Visegrády, Stephanie A. Thee, Zhiyong Wang, Chris de Graaf, Jose Brea, Maria Isabel Loza, Rob Leurs, György M. Keserű. Controlling the selectivity of aminergic GPCR ligands from the extracellular vestibule. Bioorganic Chemistry 2021, 111 , 104832. https://doi.org/10.1016/j.bioorg.2021.104832
- Youwen Zhuang, Brian Krumm, Huibing Zhang, X. Edward Zhou, Yue Wang, Xi-Ping Huang, Yongfeng Liu, Xi Cheng, Yi Jiang, Hualiang Jiang, Cheng Zhang, Wei Yi, Bryan L. Roth, Yan Zhang, H. Eric Xu. Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor. Cell Research 2021, 31
(5)
, 593-596. https://doi.org/10.1038/s41422-021-00482-0
- Youwen Zhuang, Peiyu Xu, Chunyou Mao, Lei Wang, Brian Krumm, X. Edward Zhou, Sijie Huang, Heng Liu, Xi Cheng, Xi-Ping Huang, Dan-Dan Shen, Tinghai Xu, Yong-Feng Liu, Yue Wang, Jia Guo, Yi Jiang, Hualiang Jiang, Karsten Melcher, Bryan L. Roth, Yan Zhang, Cheng Zhang, H. Eric Xu. Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Cell 2021, 184
(4)
, 931-942.e18. https://doi.org/10.1016/j.cell.2021.01.027
- Milica Radan, Jelena Bošković, Vladimir Dobričić, Olivera Čudina, Katarina Nikolić. Current computer-aided drug design methodologies in discovery of novel drug candidates for neuropsychiatric and inflammatory diseases. Arhiv za farmaciju 2021, 71
(4)
, 225-256. https://doi.org/10.5937/arhfarm71-32523
- Katrin Denzinger, Trung Ngoc Nguyen, Theresa Noonan, Gerhard Wolber, Marcel Bermudez. Biased Ligands Differentially Shape the Conformation of the Extracellular Loop Region in 5-HT2B Receptors. International Journal of Molecular Sciences 2020, 21
(24)
, 9728. https://doi.org/10.3390/ijms21249728
- Damian Kułaga, Jolanta Jaśkowska, Grzegorz Satała, Gniewomir Latacz, Paweł Śliwa. Aminotriazines with indole motif as novel, 5-HT7 receptor ligands with atypical binding mode. Bioorganic Chemistry 2020, 104 , 104254. https://doi.org/10.1016/j.bioorg.2020.104254
- Polina D. Kotova, Ekaterina N. Kochkina, Oleg O. Lyamin, Olga A. Rogachevskaja, Nina P. Korolenko, Denis S. Ivashin, Marina F. Bystrova, Natella I. Enukashvily, Stanislav S. Kolesnikov. Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner. European Journal of Pharmacology 2020, 880 , 173182. https://doi.org/10.1016/j.ejphar.2020.173182
- Miles Congreve, Chris de Graaf, Nigel A. Swain, Christopher G. Tate. Impact of GPCR Structures on Drug Discovery. Cell 2020, 181
(1)
, 81-91. https://doi.org/10.1016/j.cell.2020.03.003
- Mariama Jaiteh, Ismael Rodríguez-Espigares, Jana Selent, Jens Carlsson, . Performance of virtual screening against GPCR homology models: Impact of template selection and treatment of binding site plasticity. PLOS Computational Biology 2020, 16
(3)
, e1007680. https://doi.org/10.1371/journal.pcbi.1007680
- Christofer S. Tautermann. Current and Future Challenges in Modern Drug Discovery. 2020, 1-17. https://doi.org/10.1007/978-1-0716-0282-9_1
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