Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: 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 » 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.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [3];  [4];  [5];  [3];  [1];  [6];  [6];  [1];  [7];  [7];  [8];  [1];  [1];  [3];  [3] more »;  [9];  [1];  [7];  [1];  [3];  [7];  [1] « less
+ Show Author Affiliations
  1. Univ. of Southern California, Los Angeles, CA (United States)
  2. Univ. of North Carolina, Chapel Hill, NC (United States); Medical College of Wisconsin, Milwaukee, WI (United States)
  3. Univ. of North Carolina, Chapel Hill, NC (United States)
  4. SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., CA (United States)
  5. SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)
  6. Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Center for Free-Electron Laser Science
  7. Arizona State Univ., Tempe, AZ (United States)
  8. Univ. at Buffalo, Buffalo, NY (United States)
  9. 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.
Copy to clipboard
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
Copy to clipboard
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.
Copy to clipboard
@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}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1038/s41586-019-1141-3
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 94 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Functional MT<SUB>1</SUB> and MT<SUB>2</SUB> Melatonin Receptors in Mammals
journal, January 2005

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
  • DOI: 10.1107/S1600576714007626

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
  • DOI: 10.1107/S0021889812002312

The Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS)
journal, March 2010

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
  • DOI: 10.1016/j.jmb.2009.04.068

UniProt: the universal protein knowledgebase
journal, November 2016

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
  • DOI: 10.1007/s00441-002-0579-y

The ChEMBL bioactivity database: an update
journal, November 2013

  • Bento, A. Patrícia; Gaulton, Anna; Hersey, Anne
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1031

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
  • DOI: 10.1002/bies.201400017

Biopython: freely available Python tools for computational molecular biology and bioinformatics
journal, March 2009

Performance evaluation of amino acid substitution matrices
journal, September 1993

  • Henikoff, Steven; Henikoff, Jorja G.
  • Proteins: Structure, Function, and Genetics, Vol. 17, Issue 1
  • DOI: 10.1002/prot.340170108

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
  • DOI: 10.1016/j.jmb.2007.12.028

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
  • DOI: 10.1038/nature22035

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
  • DOI: 10.1016/j.jmb.2008.06.084

Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling
journal, February 2018

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
  • DOI: 10.1016/j.tips.2014.11.001

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
  • DOI: 10.1021/jm00086a018

Structure of the agonist-bound neurotensin receptor
journal, October 2012

  • White, Jim F.; Noinaj, Nicholas; Shibata, Yoko
  • Nature, Vol. 490, Issue 7421
  • DOI: 10.1038/nature11558

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
  • DOI: 10.1093/nar/gkr703

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
  • DOI: 10.1111/bph.14029

Microscale Fluorescent Thermal Stability Assay for Membrane Proteins
journal, March 2008

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
  • DOI: 10.1111/bph.12720

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
  • DOI: 10.1021/jm00046a006

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
  • DOI: 10.1111/bph.13536

Serial Femtosecond Crystallography of G Protein–Coupled Receptors
journal, May 2018

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
  • DOI: 10.1038/nature14035

Crystallizing membrane proteins using lipidic mesophases
journal, April 2009

Serial Femtosecond Crystallography of G Protein-Coupled Receptors
journal, December 2013

Recent developments in CrystFEL
journal, March 2016

  • White, Thomas A.; Mariani, Valerio; Brehm, Wolfgang
  • Journal of Applied Crystallography, Vol. 49, Issue 2
  • DOI: 10.1107/S1600576716004751

5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology
journal, February 2018

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
  • DOI: 10.1107/S0907444904011679

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
  • DOI: 10.1021/acs.jmedchem.5b00245

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
  • DOI: 10.1002/jcc.20945

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
  • DOI: 10.1016/j.tibs.2014.03.002

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
  • DOI: 10.1006/jmbi.1999.3488

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
  • DOI: 10.1186/1758-2946-3-33

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
  • DOI: 10.1038/ncomms4309

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
  • DOI: 10.1074/jbc.M600548200

High-Resolution Crystal Structure of an Engineered Human  2-Adrenergic G Protein-Coupled Receptor
journal, October 2007

Recent Progress in the Development of Agonists and Antagonists for Melatonin Receptors
journal, June 2012

Cloning of a melatonin-related receptor from human pituitary
journal, May 1996

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
  • DOI: 10.1038/nature10361

COBALT: constraint-based alignment tool for multiple protein sequences
journal, March 2007

Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features
journal, December 1983

Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain
journal, May 1999

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
  • DOI: 10.1107/S0907444911001314

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
  • DOI: 10.1002/jcc.540150503

Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus
journal, April 2016

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
  • DOI: 10.1006/jmbi.2000.4315

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
  • DOI: 10.1016/S0022-2836(05)80360-2

On Information and Sufficiency
journal, March 1951

  • Kullback, S.; Leibler, R. A.
  • The Annals of Mathematical Statistics, Vol. 22, Issue 1
  • DOI: 10.1214/aoms/1177729694

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
  • DOI: 10.1107/S0907444909052925

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
  • DOI: 10.1085/jgp.201511526

Melatonin
journal, March 2006

  • Hardeland, Rüdiger; Pandi-Perumal, S. R.; Cardinali, Daniel P.
  • The International Journal of Biochemistry & Cell Biology, Vol. 38, Issue 3
  • DOI: 10.1016/j.biocel.2005.08.020

CAVER Analyst 1.0: graphic tool for interactive visualization and analysis of tunnels and channels in protein structures
journal, May 2014

Ramelteon: Profile of a new sleep-promoting medication
journal, January 2006

Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography
journal, August 2014

XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity
journal, April 2019

NCBI BLAST: a better web interface
journal, May 2008

  • Johnson, M.; Zaretskaya, I.; Raytselis, Y.
  • Nucleic Acids Research, Vol. 36, Issue Web Server
  • DOI: 10.1093/nar/gkn201

The Protein Data Bank
journal, January 2000

Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin
journal, January 2003

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
  • DOI: 10.1093/nar/gkv1178

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
  • DOI: 10.1124/pr.110.002832

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
  • DOI: 10.1007/s00775-020-01814-y

High Membrane Permeability for Melatonin
journal, February 2016

PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019

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
  • DOI: 10.1038/s41467-020-16586-x

Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021

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
  • DOI: 10.1038/s41589-020-00715-0

UniProt: the Universal Protein knowledgebase
journal, January 2004

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
  • DOI: 10.1093/nar/gkw1218

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
  • DOI: 10.1107/s0907444902003451

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
  • DOI: 10.17615/5vt2-kp93

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
  • DOI: 10.17863/cam.45787

UniProt: the universal protein knowledgebase
journal, February 2018

  • UniProt Consortium, The
  • Nucleic Acids Research, Vol. 46, Issue 5
  • DOI: 10.1093/nar/gky092

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
  • DOI: 10.17615/xvss-3j42

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
  • DOI: 10.1002/jcc.21367

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
  • DOI: 10.1002/jcc.540150503

Performance evaluation of amino acid substitution matrices
journal, September 1993

  • Henikoff, Steven; Henikoff, Jorja G.
  • Proteins: Structure, Function, and Genetics, Vol. 17, Issue 1
  • DOI: 10.1002/prot.340170108

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
  • DOI: 10.1007/s00441-002-0579-y

Melatonin
journal, March 2006

  • Hardeland, Rüdiger; Pandi-Perumal, S. R.; Cardinali, Daniel P.
  • The International Journal of Biochemistry & Cell Biology, Vol. 38, Issue 3
  • DOI: 10.1016/j.biocel.2005.08.020

High Membrane Permeability for Melatonin
journal, February 2016

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
  • DOI: 10.1016/j.jmb.2009.04.068

Microscale Fluorescent Thermal Stability Assay for Membrane Proteins
journal, March 2008

Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling
journal, February 2018

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
  • DOI: 10.1016/j.tips.2014.11.001

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
  • DOI: 10.1021/acs.jmedchem.5b00245

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
  • DOI: 10.1021/jm00046a006

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
  • DOI: 10.1021/jm00086a018

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
  • DOI: 10.1038/nature10361

Structure of the agonist-bound neurotensin receptor
journal, October 2012

  • White, Jim F.; Noinaj, Nicholas; Shibata, Yoko
  • Nature, Vol. 490, Issue 7421
  • DOI: 10.1038/nature11558

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
  • DOI: 10.1038/nature14035

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
  • DOI: 10.1038/nature22035

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
  • DOI: 10.1038/ncomms4309

Crystallizing membrane proteins using lipidic mesophases
journal, April 2009

Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography
journal, August 2014

COBALT: constraint-based alignment tool for multiple protein sequences
journal, March 2007

Biopython: freely available Python tools for computational molecular biology and bioinformatics
journal, March 2009

NCBI BLAST: a better web interface
journal, May 2008

  • Johnson, M.; Zaretskaya, I.; Raytselis, Y.
  • Nucleic Acids Research, Vol. 36, Issue Web Server
  • DOI: 10.1093/nar/gkn201

The ChEMBL bioactivity database: an update
journal, November 2013

  • Bento, A. Patrícia; Gaulton, Anna; Hersey, Anne
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1031

UniProt: the universal protein knowledgebase
journal, November 2016

Indexing in single-crystal diffractometry with an obstinate list of reflections
journal, April 1992

The integration of macromolecular diffraction data
journal, December 2005

  • Leslie, Andrew G. W.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1
  • DOI: 10.1107/s0907444905039107

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
  • DOI: 10.1107/s0907444909042073

XDS
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
  • DOI: 10.1107/s0907444909047337

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
  • DOI: 10.1107/s0907444910007493

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
  • DOI: 10.1124/pr.110.002832

Serial Femtosecond Crystallography of G Protein-Coupled Receptors
journal, December 2013

Serial Femtosecond Crystallography of G Protein–Coupled Receptors
journal, May 2018

On Information and Sufficiency
journal, March 1951

  • Kullback, S.; Leibler, R. A.
  • The Annals of Mathematical Statistics, Vol. 22, Issue 1
  • DOI: 10.1214/aoms/1177729694

Ramelteon: Profile of a new sleep-promoting medication
journal, January 2006

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
  • DOI: 10.17863/cam.45787

Recent Progress in the Development of Agonists and Antagonists for Melatonin Receptors
journal, June 2012

    Sort by:
    [ × clear filter / sort ]

    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
    • DOI: 10.1002/prp2.556

    Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors
    journal, December 2019

    XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity
    journal, April 2019

    Toward G protein-coupled receptor structure-based drug design using X-ray lasers
    journal, October 2019

    Mutagenesis facilitated crystallization of GLP-1R
    journal, October 2019

    A fixed-target platform for serial femtosecond crystallography in a hydrated environment
    journal, January 2020

    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
    • DOI: 10.1111/febs.15099

    Structural insights into melatonin receptors
    journal, November 2019

    • Stauch, Benjamin; Johansson, Linda C.; Cherezov, Vadim
    • The FEBS Journal, Vol. 287, Issue 8
    • DOI: 10.1111/febs.15128

    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
    • DOI: 10.1111/jpi.12606

    Recent Advances in the Drug Discovery and Development of Dualsteric/ Bitopic Activators of G Protein-Coupled Receptors
    journal, December 2019

    Melatonin Target Proteins: Too Many or Not Enough?
    journal, November 2019

    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
    • DOI: 10.3390/ijms20184342

    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
    • DOI: 10.3204/pubdb-2019-05316

    Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors
    text, January 2019

    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
    • DOI: 10.17615/xvss-3j42

    Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors
    journal, December 2019

    A host dTMP-bound structure of T4 phage dCMP hydroxymethylase mutant using an X-ray free electron laser
    journal, November 2019

    Melatonin Target Proteins: Too Many or Not Enough?
    journal, November 2019

    COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms
    journal, March 2021

    • Malone, Robert W.; Tisdall, Philip; Fremont-Smith, Philip
    • Frontiers in Pharmacology, Vol. 12
    • DOI: 10.3389/fphar.2021.633680

    Structure-based discovery of potent and selective melatonin receptor agonists
    journal, March 2020

      Sort by:
      [ × clear filter / sort ]

      Similar Records in DOE PAGES and OSTI.GOV collections: