Structural basis of ligand recognition at the human MT1 melatonin receptor
Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that maintains circadian rhythms by synchronization to environmental cues and is involved in diverse physiological processes such as the regulation of blood pressure and core body temperature, oncogenesis, and immune function. Melatonin is formed in the pineal gland in a light-regulated manner by enzymatic conversion from 5-hydroxytryptamine (5-HT or serotonin), and modulates sleep and wakefulness5 by activating two high-affinity G-protein-coupled receptors, type 1A (MT1) and type 1B (MT2). Shift work, travel, and ubiquitous artificial lighting can disrupt natural circadian rhythms; as a result, sleep disorders affect a substantial population in modern society and pose a considerable economic burden. Over-the-counter melatonin is widely used to alleviate jet lag and as a safer alternative to benzodiazepines and other sleeping aids and is one of the most popular supplements in the United States. Here in this paper, we present high-resolution room-temperature X-ray free electron laser (XFEL) structures of MT1 in complex with four agonists: the insomnia drug ramelteon, two melatonin analogues, and the mixed melatonin–serotonin antidepressant agomelatine. The structure of MT2 is described in an accompanying paper. Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly inmore »
- Authors:
-
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- Univ. of Southern California, Los Angeles, CA (United States)
- Univ. of North Carolina, Chapel Hill, NC (United States); Medical College of Wisconsin, Milwaukee, WI (United States)
- Univ. of North Carolina, Chapel Hill, NC (United States)
- SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., CA (United States)
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)
- Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Center for Free-Electron Laser Science
- Arizona State Univ., Tempe, AZ (United States)
- Univ. at Buffalo, Buffalo, NY (United States)
- Univ. of Lille,Lille (France)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1528824
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature (London)
- Additional Journal Information:
- Journal Name: Nature (London); Journal Volume: 569; Journal Issue: 7755; Journal ID: ISSN 0028-0836
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Stauch, Benjamin, Johansson, Linda C., McCorvy, John D., Patel, Nilkanth, Han, Gye Won, Huang, Xi-Ping, Gati, Cornelius, Batyuk, Alexander, Slocum, Samuel T., Ishchenko, Andrii, Brehm, Wolfgang, White, Thomas A., Michaelian, Nairie, Madsen, Caleb, Zhu, Lan, Grant, Thomas D., Grandner, Jessica M., Shiriaeva, Anna, Olsen, Reid H. J., Tribo, Alexandra R., Yous, Saïd, Stevens, Raymond C., Weierstall, Uwe, Katritch, Vsevolod, Roth, Bryan L., Liu, Wei, and Cherezov, Vadim. Structural basis of ligand recognition at the human MT1 melatonin receptor. United States: N. p., 2019.
Web. doi:10.1038/s41586-019-1141-3.
Stauch, Benjamin, Johansson, Linda C., McCorvy, John D., Patel, Nilkanth, Han, Gye Won, Huang, Xi-Ping, Gati, Cornelius, Batyuk, Alexander, Slocum, Samuel T., Ishchenko, Andrii, Brehm, Wolfgang, White, Thomas A., Michaelian, Nairie, Madsen, Caleb, Zhu, Lan, Grant, Thomas D., Grandner, Jessica M., Shiriaeva, Anna, Olsen, Reid H. J., Tribo, Alexandra R., Yous, Saïd, Stevens, Raymond C., Weierstall, Uwe, Katritch, Vsevolod, Roth, Bryan L., Liu, Wei, & Cherezov, Vadim. Structural basis of ligand recognition at the human MT1 melatonin receptor. United States. https://doi.org/10.1038/s41586-019-1141-3
Stauch, Benjamin, Johansson, Linda C., McCorvy, John D., Patel, Nilkanth, Han, Gye Won, Huang, Xi-Ping, Gati, Cornelius, Batyuk, Alexander, Slocum, Samuel T., Ishchenko, Andrii, Brehm, Wolfgang, White, Thomas A., Michaelian, Nairie, Madsen, Caleb, Zhu, Lan, Grant, Thomas D., Grandner, Jessica M., Shiriaeva, Anna, Olsen, Reid H. J., Tribo, Alexandra R., Yous, Saïd, Stevens, Raymond C., Weierstall, Uwe, Katritch, Vsevolod, Roth, Bryan L., Liu, Wei, and Cherezov, Vadim. Wed .
"Structural basis of ligand recognition at the human MT1 melatonin receptor". United States. https://doi.org/10.1038/s41586-019-1141-3. https://www.osti.gov/servlets/purl/1528824.
@article{osti_1528824,
title = {Structural basis of ligand recognition at the human MT1 melatonin receptor},
author = {Stauch, Benjamin and Johansson, Linda C. and McCorvy, John D. and Patel, Nilkanth and Han, Gye Won and Huang, Xi-Ping and Gati, Cornelius and Batyuk, Alexander and Slocum, Samuel T. and Ishchenko, Andrii and Brehm, Wolfgang and White, Thomas A. and Michaelian, Nairie and Madsen, Caleb and Zhu, Lan and Grant, Thomas D. and Grandner, Jessica M. and Shiriaeva, Anna and Olsen, Reid H. J. and Tribo, Alexandra R. and Yous, Saïd and Stevens, Raymond C. and Weierstall, Uwe and Katritch, Vsevolod and Roth, Bryan L. and Liu, Wei and Cherezov, Vadim},
abstractNote = {Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that maintains circadian rhythms by synchronization to environmental cues and is involved in diverse physiological processes such as the regulation of blood pressure and core body temperature, oncogenesis, and immune function. Melatonin is formed in the pineal gland in a light-regulated manner by enzymatic conversion from 5-hydroxytryptamine (5-HT or serotonin), and modulates sleep and wakefulness5 by activating two high-affinity G-protein-coupled receptors, type 1A (MT1) and type 1B (MT2). Shift work, travel, and ubiquitous artificial lighting can disrupt natural circadian rhythms; as a result, sleep disorders affect a substantial population in modern society and pose a considerable economic burden. Over-the-counter melatonin is widely used to alleviate jet lag and as a safer alternative to benzodiazepines and other sleeping aids and is one of the most popular supplements in the United States. Here in this paper, we present high-resolution room-temperature X-ray free electron laser (XFEL) structures of MT1 in complex with four agonists: the insomnia drug ramelteon, two melatonin analogues, and the mixed melatonin–serotonin antidepressant agomelatine. The structure of MT2 is described in an accompanying paper. Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly in the structure and composition of their ligand pockets; in MT1, access to the ligand pocket is tightly sealed from solvent by extracellular loop 2, leaving only a narrow channel between transmembrane helices IV and V that connects it to the lipid bilayer. The binding site is extremely compact, and ligands interact with MT1 mainly by strong aromatic stacking with Phe179 and auxiliary hydrogen bonds with Asn162 and Gln181. Our structures provide an unexpected example of atypical ligand entry for a non-lipid receptor, lay the molecular foundation of ligand recognition by melatonin receptors, and will facilitate the design of future tool compounds and therapeutic agents, while their comparison to 5-HT receptors yields insights into the evolution and polypharmacology of G-protein-coupled receptors.},
doi = {10.1038/s41586-019-1141-3},
journal = {Nature (London)},
number = 7755,
volume = 569,
place = {United States},
year = {Wed Apr 24 00:00:00 EDT 2019},
month = {Wed Apr 24 00:00:00 EDT 2019}
}
Web of Science
Works referenced in this record:
Functional MT<SUB>1</SUB> and MT<SUB>2</SUB> Melatonin Receptors in Mammals
journal, January 2005
- Dubocovich, Margarita L.; Markowska, Magdalena
- Endocrine, Vol. 27, Issue 2
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors
book, January 1995
- Ballesteros, Juan A.; Weinstein, Harel
- Receptor Molecular Biology, Vol. 25, p. 366-428
Cheetah : software for high-throughput reduction and analysis of serial femtosecond X-ray diffraction data
journal, May 2014
- Barty, Anton; Kirian, Richard A.; Maia, Filipe R. N. C.
- Journal of Applied Crystallography, Vol. 47, Issue 3
CrystFEL : a software suite for snapshot serial crystallography
journal, March 2012
- White, Thomas A.; Kirian, Richard A.; Martin, Andrew V.
- Journal of Applied Crystallography, Vol. 45, Issue 2
The Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS)
journal, March 2010
- Boutet, Sébastien; J. Williams, Garth
- New Journal of Physics, Vol. 12, Issue 3
Thermostabilization of the Neurotensin Receptor NTS1
journal, July 2009
- Shibata, Yoko; White, Jim F.; Serrano-Vega, Maria J.
- Journal of Molecular Biology, Vol. 390, Issue 2
UniProt: the universal protein knowledgebase
journal, November 2016
- :(unav),
- Nucleic Acids Research, Vol. 45, Issue D1, p. D158-D169
Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation
journal, July 2002
- Ganguly, Surajit; Coon, Steven L.; Klein, David C.
- Cell and Tissue Research, Vol. 309, Issue 1
The ChEMBL bioactivity database: an update
journal, November 2013
- Bento, A. Patrícia; Gaulton, Anna; Hersey, Anne
- Nucleic Acids Research, Vol. 42, Issue D1
Understanding melatonin receptor pharmacology: Latest insights from mouse models, and their relevance to human disease: Prospects & Overviews
journal, June 2014
- Tosini, Gianluca; Owino, Sharon; Guillaume, Jean-Luc
- BioEssays, Vol. 36, Issue 8
Biopython: freely available Python tools for computational molecular biology and bioinformatics
journal, March 2009
- Cock, P. J. A.; Antao, T.; Chang, J. T.
- Bioinformatics, Vol. 25, Issue 11
Performance evaluation of amino acid substitution matrices
journal, September 1993
- Henikoff, Steven; Henikoff, Jorja G.
- Proteins: Structure, Function, and Genetics, Vol. 17, Issue 1
Stabilization of the Human β2-Adrenergic Receptor TM4–TM3–TM5 Helix Interface by Mutagenesis of Glu1223.41, A Critical Residue in GPCR Structure
journal, March 2008
- Roth, Christopher B.; Hanson, Michael A.; Stevens, Raymond C.
- Journal of Molecular Biology, Vol. 376, Issue 5
Structural basis for selectivity and diversity in angiotensin II receptors
journal, April 2017
- Zhang, Haitao; Han, Gye Won; Batyuk, Alexander
- Nature, Vol. 544, Issue 7650
Agonist-Induced Conformational Changes in Bovine Rhodopsin: Insight into Activation of G-Protein-Coupled Receptors
journal, October 2008
- Bhattacharya, Supriyo; Hall, Spencer E.; Vaidehi, Nagarajan
- Journal of Molecular Biology, Vol. 382, Issue 2
Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling
journal, February 2018
- White, Kate L.; Eddy, Matthew T.; Gao, Zhan-Guo
- Structure, Vol. 26, Issue 2
Generic GPCR residue numbers – aligning topology maps while minding the gaps
journal, January 2015
- Isberg, Vignir; de Graaf, Chris; Bortolato, Andrea
- Trends in Pharmacological Sciences, Vol. 36, Issue 1
Novel naphthalenic ligands with high affinity for the melatonin receptor
journal, April 1992
- Yous, S.; Andrieux, J.; Howell, H. E.
- Journal of Medicinal Chemistry, Vol. 35, Issue 8
Structure of the agonist-bound neurotensin receptor
journal, October 2012
- White, Jim F.; Noinaj, Nicholas; Shibata, Yoko
- Nature, Vol. 490, Issue 7421
OPM database and PPM web server: resources for positioning of proteins in membranes
journal, September 2011
- Lomize, Mikhail A.; Pogozheva, Irina D.; Joo, Hyeon
- Nucleic Acids Research, Vol. 40, Issue D1
Importance of the second extracellular loop for melatonin MT 1 receptor function and absence of melatonin binding in GPR50 : E2 loop in MT
journal, October 2017
- Clement, Nathalie; Renault, Nicolas; Guillaume, Jean-Luc
- British Journal of Pharmacology, Vol. 175, Issue 16
Microscale Fluorescent Thermal Stability Assay for Membrane Proteins
journal, March 2008
- Alexandrov, Alexander I.; Mileni, Mauro; Chien, Ellen Y. T.
- Structure, Vol. 16, Issue 3
Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties: Pharmacological properties of the antidepressant agomelatine
journal, July 2014
- Guardiola-Lemaitre, B.; De Bodinat, C.; Delagrange, P.
- British Journal of Pharmacology, Vol. 171, Issue 15
Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands
journal, September 1994
- Depreux, Patrick; Lesieur, Daniel; Mansour, Hamid Ait
- Journal of Medicinal Chemistry, Vol. 37, Issue 20
Update on melatonin receptors: IUPHAR Review 20: Melatonin receptors
journal, August 2016
- Jockers, Ralf; Delagrange, Philippe; Dubocovich, Margarita L.
- British Journal of Pharmacology, Vol. 173, Issue 18
Serial Femtosecond Crystallography of G Protein–Coupled Receptors
journal, May 2018
- Stauch, Benjamin; Cherezov, Vadim
- Annual Review of Biophysics, Vol. 47, Issue 1
Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant
journal, December 2014
- Yin, Jie; Mobarec, Juan Carlos; Kolb, Peter
- Nature, Vol. 519, Issue 7542
Crystallizing membrane proteins using lipidic mesophases
journal, April 2009
- Caffrey, Martin; Cherezov, Vadim
- Nature Protocols, Vol. 4, Issue 5
Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94
journal, April 1996
- Halgren, Thomas A.
- Journal of Computational Chemistry, Vol. 17, Issue 5-6
Serial Femtosecond Crystallography of G Protein-Coupled Receptors
journal, December 2013
- Liu, W.; Wacker, D.; Gati, C.
- Science, Vol. 342, Issue 6165
Recent developments in CrystFEL
journal, March 2016
- White, Thomas A.; Mariani, Valerio; Brehm, Wolfgang
- Journal of Applied Crystallography, Vol. 49, Issue 2
5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology
journal, February 2018
- Peng, Yao; McCorvy, John D.; Harpsøe, Kasper
- Cell, Vol. 172, Issue 4
PRODRG : a tool for high-throughput crystallography of protein–ligand complexes
journal, July 2004
- Schüttelkopf, Alexander W.; van Aalten, Daan M. F.
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 8
Novel N -Acetyl Bioisosteres of Melatonin: Melatonergic Receptor Pharmacology, Physicochemical Studies, and Phenotypic Assessment of Their Neurogenic Potential
journal, March 2015
- de la Fuente Revenga, Mario; Fernández-Sáez, Nerea; Herrera-Arozamena, Clara
- Journal of Medicinal Chemistry, Vol. 58, Issue 12
CHARMM-GUI: A web-based graphical user interface for CHARMM
journal, March 2008
- Jo, Sunhwan; Kim, Taehoon; Iyer, Vidyashankara G.
- Journal of Computational Chemistry, Vol. 29, Issue 11
Allosteric sodium in class A GPCR signaling
journal, May 2014
- Katritch, Vsevolod; Fenalti, Gustavo; Abola, Enrique E.
- Trends in Biochemical Sciences, Vol. 39, Issue 5
Statistical analysis of amino acid patterns in transmembrane helices: the GxxxG motif occurs frequently and in association with β-branched residues at neighboring positions
journal, February 2000
- Senes, Alessandro; Gerstein, Mark; Engelman, Donald M.
- Journal of Molecular Biology, Vol. 296, Issue 3
Open Babel: An open chemical toolbox
journal, October 2011
- O'Boyle, Noel M.; Banck, Michael; James, Craig A.
- Journal of Cheminformatics, Vol. 3, Issue 1
The Novel Melatonin Agonist Agomelatine (S20098) Is an Antagonist at 5-Hydroxytryptamine 2C Receptors, Blockade of Which Enhances the Activity of Frontocortical Dopaminergic and Adrenergic Pathways
journal, May 2003
- Millan, M. J.; Gobert, A.; Lejeune, F.
- Journal of Pharmacology and Experimental Therapeutics, Vol. 306, Issue 3
Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography
journal, February 2014
- Weierstall, Uwe; James, Daniel; Wang, Chong
- Nature Communications, Vol. 5, Issue 1
Genetic Analysis of the First and Third Extracellular Loops of the C5a Receptor Reveals an Essential W X FG Motif in the First Loop
journal, February 2006
- Klco, Jeffery M.; Nikiforovich, Gregory V.; Baranski, Thomas J.
- Journal of Biological Chemistry, Vol. 281, Issue 17
High-Resolution Crystal Structure of an Engineered Human 2-Adrenergic G Protein-Coupled Receptor
journal, October 2007
- Cherezov, V.; Rosenbaum, D. M.; Hanson, M. A.
- Science, Vol. 318, Issue 5854
Recent Progress in the Development of Agonists and Antagonists for Melatonin Receptors
journal, June 2012
- P. Zlotos, D.
- Current Medicinal Chemistry, Vol. 19, Issue 21
Cloning of a melatonin-related receptor from human pituitary
journal, May 1996
- Reppert, Steven M.; Weaver, David R.; Ebisawa, Takashi
- FEBS Letters, Vol. 386, Issue 2-3
Crystal structure of the β2 adrenergic receptor–Gs protein complex
journal, July 2011
- Rasmussen, Søren G. F.; DeVree, Brian T.; Zou, Yaozhong
- Nature, Vol. 477, Issue 7366
COBALT: constraint-based alignment tool for multiple protein sequences
journal, March 2007
- Papadopoulos, J. S.; Agarwala, R.
- Bioinformatics, Vol. 23, Issue 9
Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features
journal, December 1983
- Kabsch, Wolfgang; Sander, Christian
- Biopolymers, Vol. 22, Issue 12
Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain
journal, May 1999
- Pasqualetti, M.; Ori, M.; Castagna, M.
- Neuroscience, Vol. 92, Issue 2
REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011
- Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
ICM?A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation
journal, May 1994
- Abagyan, Ruben; Totrov, Maxim; Kuznetsov, Dmitry
- Journal of Computational Chemistry, Vol. 15, Issue 5
Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus
journal, April 2016
- Pévet, Paul
- Expert Opinion on Therapeutic Targets, Vol. 20, Issue 10
Predicting transmembrane protein topology with a hidden markov model: application to complete genomes11Edited by F. Cohen
journal, January 2001
- Krogh, Anders; Larsson, Björn; von Heijne, Gunnar
- Journal of Molecular Biology, Vol. 305, Issue 3
Basic local alignment search tool
journal, October 1990
- Altschul, Stephen F.; Gish, Warren; Miller, Webb
- Journal of Molecular Biology, Vol. 215, Issue 3, p. 403-410
On Information and Sufficiency
journal, March 1951
- Kullback, S.; Leibler, R. A.
- The Annals of Mathematical Statistics, Vol. 22, Issue 1
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
High membrane permeability for melatonin
journal, December 2015
- Yu, Haijie; Dickson, Eamonn J.; Jung, Seung-Ryoung
- The Journal of General Physiology, Vol. 147, Issue 1
Melatonin
journal, March 2006
- Hardeland, Rüdiger; Pandi-Perumal, S. R.; Cardinali, Daniel P.
- The International Journal of Biochemistry & Cell Biology, Vol. 38, Issue 3
CAVER Analyst 1.0: graphic tool for interactive visualization and analysis of tunnels and channels in protein structures
journal, May 2014
- Kozlikova, Barbora; Sebestova, Eva; Sustr, Vilem
- Bioinformatics, Vol. 30, Issue 18
Ramelteon: Profile of a new sleep-promoting medication
journal, January 2006
- Owen, R. T.
- Drugs of Today, Vol. 42, Issue 4
Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography
journal, August 2014
- Liu, Wei; Ishchenko, Andrii; Cherezov, Vadim
- Nature Protocols, Vol. 9, Issue 9
XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity
journal, April 2019
- Johansson, Linda C.; Stauch, Benjamin; McCorvy, John D.
- Nature, Vol. 569, Issue 7755
NCBI BLAST: a better web interface
journal, May 2008
- Johnson, M.; Zaretskaya, I.; Raytselis, Y.
- Nucleic Acids Research, Vol. 36, Issue Web Server
Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin
journal, January 2003
- Tan, Dun-Xian; Manchester, Lucien C.; Hardeland, Rudiger
- Journal of Pineal Research, Vol. 34, Issue 1
GPCRdb: an information system for G protein-coupled receptors
journal, November 2015
- Isberg, Vignir; Mordalski, Stefan; Munk, Christian
- Nucleic Acids Research, Vol. 44, Issue D1
International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors
journal, July 2010
- Dubocovich, Margarita L.; Delagrange, Philippe; Krause, Diana N.
- Pharmacological Reviews, Vol. 62, Issue 3
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen
journal, August 2020
- Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe
- JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6
High Membrane Permeability for Melatonin
journal, February 2016
- Yu, Haijie; Dickson, Eamonn; Jung, Seung-Ryoung
- Biophysical Journal, Vol. 110, Issue 3
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019
- Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman
- Nature Communications, Vol. 10, Issue 1
Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release
journal, June 2020
- Bailey, Henry J.; Bezerra, Gustavo A.; Marcero, Jason R.
- Nature Communications, Vol. 11, Issue 1
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021
- Tillu, Vikas A.; Rae, James; Gao, Ya
- Nature Communications, Vol. 12, Issue 1
Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance
journal, January 2021
- Svetlov, Maxim S.; Syroegin, Egor A.; Aleksandrova, Elena V.
- Nature Chemical Biology, Vol. 17, Issue 4
UniProt: the Universal Protein knowledgebase
journal, January 2004
- Apweiler, R.
- Nucleic Acids Research, Vol. 32, Issue 90001
GPCRdb: an information system for G protein-coupled receptors
journal, December 2016
- Isberg, Vignir; Mordalski, Stefan; Munk, Christian
- Nucleic Acids Research, Vol. 45, Issue 5
The Protein Data Bank
journal, May 2002
- Berman, Helen M.; Battistuz, Tammy; Bhat, T. N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 6
Allosteric sodium in class A GPCR signaling
text, January 2014
- Vsevolod, Katritch,; Vadim, Cherezov,; C., Stevens, Raymond
- The University of North Carolina at Chapel Hill University Libraries
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository
UniProt: the universal protein knowledgebase
journal, February 2018
- UniProt Consortium, The
- Nucleic Acids Research, Vol. 46, Issue 5
XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity
text, January 2019
- G. W., Han,; S. T., Slocum,; X. -P., Huang,
- Nature Publishing Group
CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields
journal, January 2009
- Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.
- Journal of Computational Chemistry
ICM?A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation
journal, May 1994
- Abagyan, Ruben; Totrov, Maxim; Kuznetsov, Dmitry
- Journal of Computational Chemistry, Vol. 15, Issue 5
Performance evaluation of amino acid substitution matrices
journal, September 1993
- Henikoff, Steven; Henikoff, Jorja G.
- Proteins: Structure, Function, and Genetics, Vol. 17, Issue 1
Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation
journal, July 2002
- Ganguly, Surajit; Coon, Steven L.; Klein, David C.
- Cell and Tissue Research, Vol. 309, Issue 1
Melatonin
journal, March 2006
- Hardeland, Rüdiger; Pandi-Perumal, S. R.; Cardinali, Daniel P.
- The International Journal of Biochemistry & Cell Biology, Vol. 38, Issue 3
High Membrane Permeability for Melatonin
journal, February 2016
- Yu, Haijie; Dickson, Eamonn; Jung, Seung-Ryoung
- Biophysical Journal, Vol. 110, Issue 3
Thermostabilization of the Neurotensin Receptor NTS1
journal, July 2009
- Shibata, Yoko; White, Jim F.; Serrano-Vega, Maria J.
- Journal of Molecular Biology, Vol. 390, Issue 2
Microscale Fluorescent Thermal Stability Assay for Membrane Proteins
journal, March 2008
- Alexandrov, Alexander I.; Mileni, Mauro; Chien, Ellen Y. T.
- Structure, Vol. 16, Issue 3
Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling
journal, February 2018
- White, Kate L.; Eddy, Matthew T.; Gao, Zhan-Guo
- Structure, Vol. 26, Issue 2
Generic GPCR residue numbers – aligning topology maps while minding the gaps
journal, January 2015
- Isberg, Vignir; de Graaf, Chris; Bortolato, Andrea
- Trends in Pharmacological Sciences, Vol. 36, Issue 1
Novel N -Acetyl Bioisosteres of Melatonin: Melatonergic Receptor Pharmacology, Physicochemical Studies, and Phenotypic Assessment of Their Neurogenic Potential
journal, March 2015
- de la Fuente Revenga, Mario; Fernández-Sáez, Nerea; Herrera-Arozamena, Clara
- Journal of Medicinal Chemistry, Vol. 58, Issue 12
Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands
journal, September 1994
- Depreux, Patrick; Lesieur, Daniel; Mansour, Hamid Ait
- Journal of Medicinal Chemistry, Vol. 37, Issue 20
Novel naphthalenic ligands with high affinity for the melatonin receptor
journal, April 1992
- Yous, S.; Andrieux, J.; Howell, H. E.
- Journal of Medicinal Chemistry, Vol. 35, Issue 8
Crystal structure of the β2 adrenergic receptor–Gs protein complex
journal, July 2011
- Rasmussen, Søren G. F.; DeVree, Brian T.; Zou, Yaozhong
- Nature, Vol. 477, Issue 7366
Structure of the agonist-bound neurotensin receptor
journal, October 2012
- White, Jim F.; Noinaj, Nicholas; Shibata, Yoko
- Nature, Vol. 490, Issue 7421
Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant
journal, December 2014
- Yin, Jie; Mobarec, Juan Carlos; Kolb, Peter
- Nature, Vol. 519, Issue 7542
Structural basis for selectivity and diversity in angiotensin II receptors
journal, April 2017
- Zhang, Haitao; Han, Gye Won; Batyuk, Alexander
- Nature, Vol. 544, Issue 7650
Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography
journal, February 2014
- Weierstall, Uwe; James, Daniel; Wang, Chong
- Nature Communications, Vol. 5, Issue 1
Crystallizing membrane proteins using lipidic mesophases
journal, April 2009
- Caffrey, Martin; Cherezov, Vadim
- Nature Protocols, Vol. 4, Issue 5
Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography
journal, August 2014
- Liu, Wei; Ishchenko, Andrii; Cherezov, Vadim
- Nature Protocols, Vol. 9, Issue 9
COBALT: constraint-based alignment tool for multiple protein sequences
journal, March 2007
- Papadopoulos, J. S.; Agarwala, R.
- Bioinformatics, Vol. 23, Issue 9
Biopython: freely available Python tools for computational molecular biology and bioinformatics
journal, March 2009
- Cock, P. J. A.; Antao, T.; Chang, J. T.
- Bioinformatics, Vol. 25, Issue 11
NCBI BLAST: a better web interface
journal, May 2008
- Johnson, M.; Zaretskaya, I.; Raytselis, Y.
- Nucleic Acids Research, Vol. 36, Issue Web Server
The ChEMBL bioactivity database: an update
journal, November 2013
- Bento, A. Patrícia; Gaulton, Anna; Hersey, Anne
- Nucleic Acids Research, Vol. 42, Issue D1
UniProt: the universal protein knowledgebase
journal, November 2016
- :(unav),
- Nucleic Acids Research, Vol. 45, Issue D1, p. D158-D169
Indexing in single-crystal diffractometry with an obstinate list of reflections
journal, April 1992
- Duisenberg, A. J. M.
- Journal of Applied Crystallography, Vol. 25, Issue 2
The integration of macromolecular diffraction data
journal, December 2005
- Leslie, Andrew G. W.
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1
MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009
- Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors
journal, July 2010
- Dubocovich, Margarita L.; Delagrange, Philippe; Krause, Diana N.
- Pharmacological Reviews, Vol. 62, Issue 3
Serial Femtosecond Crystallography of G Protein-Coupled Receptors
journal, December 2013
- Liu, W.; Wacker, D.; Gati, C.
- Science, Vol. 342, Issue 6165
Serial Femtosecond Crystallography of G Protein–Coupled Receptors
journal, May 2018
- Stauch, Benjamin; Cherezov, Vadim
- Annual Review of Biophysics, Vol. 47, Issue 1
On Information and Sufficiency
journal, March 1951
- Kullback, S.; Leibler, R. A.
- The Annals of Mathematical Statistics, Vol. 22, Issue 1
Ramelteon: Profile of a new sleep-promoting medication
journal, January 2006
- Owen, R. T.
- Drugs of Today, Vol. 42, Issue 4
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository
Recent Progress in the Development of Agonists and Antagonists for Melatonin Receptors
journal, June 2012
- P. Zlotos, D.
- Current Medicinal Chemistry, Vol. 19, Issue 21
Works referencing / citing this record:
The five dimensions of receptor pharmacology exemplified by melatonin receptors: An opinion
journal, December 2019
- Boutin, Jean A.; Legros, Céline
- Pharmacology Research & Perspectives, Vol. 8, Issue 1
Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors
journal, December 2019
- Gusach, Anastasiia; Luginina, Aleksandra; Marin, Egor
- Nature Communications, Vol. 10, Issue 1
XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity
journal, April 2019
- Johansson, Linda C.; Stauch, Benjamin; McCorvy, John D.
- Nature, Vol. 569, Issue 7755
Toward G protein-coupled receptor structure-based drug design using X-ray lasers
journal, October 2019
- Ishchenko, Andrii; Stauch, Benjamin; Han, Gye Won
- IUCrJ, Vol. 6, Issue 6
Mutagenesis facilitated crystallization of GLP-1R
journal, October 2019
- Xu, Yueming; Wang, Yuxia; Wang, Yang
- IUCrJ, Vol. 6, Issue 6
A fixed-target platform for serial femtosecond crystallography in a hydrated environment
journal, January 2020
- Shelby, M. L.; Gilbile, D.; Grant, T. D.
- IUCrJ, Vol. 7, Issue 1
A guide to sample delivery systems for serial crystallography
journal, August 2019
- Zhao, Feng‐Zhu; Zhang, Bin; Yan, Er‐Kai
- The FEBS Journal, Vol. 286, Issue 22
Structural insights into melatonin receptors
journal, November 2019
- Stauch, Benjamin; Johansson, Linda C.; Cherezov, Vadim
- The FEBS Journal, Vol. 287, Issue 8
Melatonin receptor structures shed new light on melatonin research
journal, September 2019
- Cecon, Erika; Liu, Lei; Jockers, Ralf
- Journal of Pineal Research, Vol. 67, Issue 4
Recent Advances in the Drug Discovery and Development of Dualsteric/ Bitopic Activators of G Protein-Coupled Receptors
journal, December 2019
- Reinecke, Bethany A.; Wang, Huiqun; Zhang, Yan
- Current Topics in Medicinal Chemistry, Vol. 19, Issue 26
Melatonin Target Proteins: Too Many or Not Enough?
journal, November 2019
- Liu, Lei; Labani, Nedjma; Cecon, Erika
- Frontiers in Endocrinology, Vol. 10
Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use
journal, September 2019
- Baltatu, Ovidiu Constantin; Senar, Sergio; Campos, Luciana Aparecida
- International Journal of Molecular Sciences, Vol. 20, Issue 18
A fixed-target platform for serial femtosecond crystallography in a hydrated environment
text, January 2020
- Shelby, M. L.; Gilbile, D.; Grant, T. D.
- Deutsches Elektronen-Synchrotron, DESY, Hamburg
Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors
text, January 2019
- Gusach, Anastasiia; Luginina, Aleksandra; Marin, Egor
- RWTH Aachen University
XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity
text, January 2019
- G. W., Han,; S. T., Slocum,; X. -P., Huang,
- Nature Publishing Group
Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors
journal, December 2019
- Gusach, Anastasiia; Luginina, Aleksandra; Marin, Egor
- Nature Communications, Vol. 10, Issue 1
A host dTMP-bound structure of T4 phage dCMP hydroxymethylase mutant using an X-ray free electron laser
journal, November 2019
- Park, Si Hoon; Park, Jaehyun; Lee, Sang Jae
- Scientific Reports, Vol. 9, Issue 1
Melatonin Target Proteins: Too Many or Not Enough?
journal, November 2019
- Liu, Lei; Labani, Nedjma; Cecon, Erika
- Frontiers in Endocrinology, Vol. 10
COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms
journal, March 2021
- Malone, Robert W.; Tisdall, Philip; Fremont-Smith, Philip
- Frontiers in Pharmacology, Vol. 12
Structure-based discovery of potent and selective melatonin receptor agonists
journal, March 2020
- Patel, Nilkanth; Huang, Xi Ping; Grandner, Jessica M.
- eLife, Vol. 9