Structural basis for selectivity and diversity in angiotensin II receptors

Zhang, Haitao; Han, Gye Won; Batyuk, Alexander; Ishchenko, Andrii; White, Kate L.; Patel, Nilkanth; Sadybekov, Anastasiia; Zamlynny, Beata; Rudd, Michael T.; Hollenstein, Kaspar; Tolstikova, Alexandra; White, Thomas A.; Hunter, Mark S.; Weierstall, Uwe; Liu, Wei; Babaoglu, Kerim; Moore, Eric L.; Katz, Ryan D.; Shipman, Jennifer M.; Garcia-Calvo, Margarita; Sharma, Sujata; Sheth, Payal; Soisson, Stephen M.; Stevens, Raymond C.; Katritch, Vsevolod; Cherezov, Vadim

doi:10.1038/nature22035

Title: Structural basis for selectivity and diversity in angiotensin II receptors

Journal Article · Thu Apr 20 00:00:00 EDT 2017 · Nature (London)

DOI:https://doi.org/10.1038/nature22035· OSTI ID:1361139

Zhang, Haitao ^[1]; Han, Gye Won ^[2]; Batyuk, Alexander ^[3]; Ishchenko, Andrii ^[2]; White, Kate L. ^[2]; Patel, Nilkanth ^[2]; Sadybekov, Anastasiia ^[2]; Zamlynny, Beata ^[4]; Rudd, Michael T. ^[5]; Hollenstein, Kaspar ^[5]; Tolstikova, Alexandra ^[6]; White, Thomas A. ^[7]; Hunter, Mark S. ^[3]; Weierstall, Uwe ^[8]; Liu, Wei ^[8]; Babaoglu, Kerim ^[5]; Moore, Eric L. ^[5]; Katz, Ryan D. ^[9]; Shipman, Jennifer M. ^[9]; Garcia-Calvo, Margarita ^[4] more »

Univ. of Southern California, Los Angeles, CA (United States); Zhejiang Univ., Zhejiang (China)
Univ. of Southern California, Los Angeles, CA (United States)
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Merck & Co., Inc., Kenilworth, NJ (United States)
Merck & Co., Inc., West Point, PA (United States)
Univ. of Hamburg, Hamburg (Germany); Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
Arizona State Univ., Tempe, AZ (United States)
Merck & Co., Inc., North Wales, PA (United States)

The angiotensin II receptors AT₁R and AT₂R serve as key components of the renin–angiotensin–aldosterone system. AT₁R has a central role in the regulation of blood pressure, but the function of AT₂R is unclear and it has a variety of reported effects. To identify the mechanisms that underlie the differences in function and ligand selectivity between these receptors, here we report crystal structures of human AT₂R bound to an AT₂R-selective ligand and to an AT₁R/AT₂R dual ligand, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G proteins or β-arrestins, in agreement with the lack of signalling responses in standard cellular assays. Structure–activity relationship, docking and mutagenesis studies revealed the crucial interactions for ligand binding and selectivity. Finally, our results thus provide insights into the structural basis of the distinct functions of the angiotensin receptors, and may guide the design of new selective ligands.

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Research Organization:: SLAC National Accelerator Lab. (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1361139

Journal Information:: Nature (London), Vol. 544, Issue 7650; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 145 works

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References (70)

The SAR of 6-(N-alkyl-N-acyl)-2-propyl-3-[(2′-tetrazol-5-yl)biphen-4-yl)methyl]-quinazolinones as balanced affinity antagonists of the human AT1 and AT2 receptors de Laszlo, Stephen E.; Chang, Raymond S.; Chen, Tsing-Bau Bioorganic & Medicinal Chemistry Letters, Vol. 5, Issue 13 https://doi.org/10.1016/0960-894X(95)00224-H	journal	July 1995
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors Ballesteros, Juan A.; Weinstein, Harel Receptor Molecular Biology, Vol. 25, p. 366-428 https://doi.org/10.1016/S1043-9471(05)80049-7	book	January 1995
Tactical Approaches to Interconverting GPCR Agonists and Antagonists Dosa, Peter I.; Amin, Elizabeth Ambrose Journal of Medicinal Chemistry, Vol. 59, Issue 3 https://doi.org/10.1021/acs.jmedchem.5b00982	journal	September 2015
Angiotensin II type 1 and type 2 receptors bind angiotensin II through different types of epitope recognition Miura, Shin-ichiro; Karnik, Sadashiva S. Journal of Hypertension, Vol. 17, Issue 3 https://doi.org/10.1097/00004872-199917030-00013	journal	January 1999
Angiotensin II Type 1 and Type 2 Receptor-induced Cell Signaling Akazawa, Hiroshi; Yano, Masamichi; Yabumoto, Chizuru Current Pharmaceutical Design, Vol. 19, Issue 17 https://doi.org/10.2174/1381612811319170003	journal	April 2013
Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser Kang, Yanyong; Zhou, X. Edward; Gao, Xiang Nature, Vol. 523, Issue 7562 https://doi.org/10.1038/nature14656	journal	July 2015
The Angiotensin II Type 2 Receptor in Brain Functions: An Update Guimond, Marie-Odile; Gallo-Payet, Nicole International Journal of Hypertension, Vol. 2012 https://doi.org/10.1155/2012/351758	journal	January 2012
Drugs targeting the renin–angiotensin–aldosterone system Zaman, Mohammad Amin; Oparil, Suzanne; Calhoun, David A. Nature Reviews Drug Discovery, Vol. 1, Issue 8 https://doi.org/10.1038/nrd873	journal	August 2002
The angiotensin II type 2 (AT2) receptor: an enigmatic seven transmembrane receptor Porrello, Enzo, R. Frontiers in Bioscience, Vol. Volume, Issue 14 https://doi.org/10.2741/3289	journal	January 2009
Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region Venkatakrishnan, A. J.; Deupi, Xavier; Lebon, Guillaume Nature, Vol. 536, Issue 7617 https://doi.org/10.1038/nature19107	journal	August 2016
Angiotensin II Activates Nuclear Transcription Factor κB Through AT ₁ and AT ₂ in Vascular Smooth Muscle Cells : Molecular Mechanisms Ruiz-Ortega, Marta; Lorenzo, Oscar; Rupérez, Mónica Circulation Research, Vol. 86, Issue 12 https://doi.org/10.1161/01.RES.86.12.1266	journal	June 2000
Intracellular Trafficking of Angiotensin II and its AT ₁ and AT ₂ Receptors: Evidence for Selective Sorting of Receptor and Ligand Hein, Lutz; Meinel, Lorenz; Pratt, Richard E. Molecular Endocrinology, Vol. 11, Issue 9 https://doi.org/10.1210/mend.11.9.9975	journal	August 1997
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation Hess, Berk Journal of Chemical Theory and Computation, Vol. 4, Issue 1 https://doi.org/10.1021/ct700200b	journal	December 2007
Constitutive Activity in the Angiotensin II Type 1 Receptor: Discovery and Applications Unal, Hamiyet; Karnik, Sadashiva S. Advances in Pharmacology https://doi.org/10.1016/B978-0-12-417197-8.00006-7	book	January 2014
Structural determinants for binding, activation, and functional selectivity of the angiotensin AT1 receptor Balakumar, P.; Jagadeesh, G. Journal of Molecular Endocrinology, Vol. 53, Issue 2 https://doi.org/10.1530/JME-14-0125	journal	July 2014
L-161,638: A potent AT2selective quinazolinone angiotensin II binding inhibitor Glinka, Tomasz W.; de Laszlo, Stephen E.; Tran, Jenifer Bioorganic & Medicinal Chemistry Letters, Vol. 4, Issue 12 https://doi.org/10.1016/S0960-894X(01)80517-5	journal	June 1994
Fusion Partner Toolchest for the Stabilization and Crystallization of G Protein-Coupled Receptors Chun, Eugene; Thompson, Aaron A.; Liu, Wei Structure, Vol. 20, Issue 6 https://doi.org/10.1016/j.str.2012.04.010	journal	June 2012
GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers Abraham, Mark James; Murtola, Teemu; Schulz, Roland SoftwareX, Vol. 1-2 https://doi.org/10.1016/j.softx.2015.06.001	journal	September 2015
Crystallizing membrane proteins using lipidic mesophases Caffrey, Martin; Cherezov, Vadim Nature Protocols, Vol. 4, Issue 5 https://doi.org/10.1038/nprot.2009.31	journal	April 2009
Calculation of an OMIT map Bhat, T. N. Journal of Applied Crystallography, Vol. 21, Issue 3 https://doi.org/10.1107/S0021889887012755	journal	June 1988
Ligand-independent signals from angiotensin II type 2 receptor induce apoptosis Miura, Shin-ichiro; Karnik, Sadashiva S. The EMBO Journal, Vol. 19, Issue 15 https://doi.org/10.1093/emboj/19.15.4026	journal	August 2000
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Analysis of full and partial agonists binding to β2-adrenergic receptor suggests a role of transmembrane helix V in agonist-specific conformational changes Katritch, Vsevolod; Reynolds, Kimberly A.; Cherezov, Vadim Journal of Molecular Recognition, Vol. 22, Issue 4 https://doi.org/10.1002/jmr.949	journal	April 2009
Structure-Function of the G Protein–Coupled Receptor Superfamily Katritch, Vsevolod; Cherezov, Vadim; Stevens, Raymond C. Annual Review of Pharmacology and Toxicology, Vol. 53, Issue 1 https://doi.org/10.1146/annurev-pharmtox-032112-135923	journal	January 2013
Serial Femtosecond Crystallography of G Protein-Coupled Receptors Liu, W.; Wacker, D.; Gati, C. Science, Vol. 342, Issue 6165 https://doi.org/10.1126/science.1244142	journal	December 2013
Structural Features for Functional Selectivity at Serotonin Receptors Wacker, D.; Wang, C.; Katritch, V. Science, Vol. 340, Issue 6132 https://doi.org/10.1126/science.1232808	journal	March 2013
Molecular mechanisms of the antagonistic action between AT1 and AT2 receptors Miura, Shin-ichiro; Matsuo, Yoshino; Kiya, Yoshihiro Biochemical and Biophysical Research Communications, Vol. 391, Issue 1 https://doi.org/10.1016/j.bbrc.2009.11.008	journal	January 2010
Recent developments in CrystFEL White, Thomas A.; Mariani, Valerio; Brehm, Wolfgang Journal of Applied Crystallography, Vol. 49, Issue 2 https://doi.org/10.1107/S1600576716004751	journal	March 2016
A Small Molecule Angiotensin II Type 2 Receptor (AT ₂ R) Antagonist Produces Analgesia in a Rat Model of Neuropathic Pain by Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) and p44/p42 MAPK Activation in the Dorsal Root Ganglia Smith, Maree T.; Woodruff, Trent M.; Wyse, Bruce D. Pain Medicine, Vol. 14, Issue 10 https://doi.org/10.1111/pme.12157	journal	October 2013
How does angiotensin AT2 receptor activation help neuronal differentiation and improve neuronal pathological situations? Guimond, Marie-Odile; Gallo-Payet, Nicole Frontiers in Endocrinology, Vol. 3 https://doi.org/10.3389/fendo.2012.00164	journal	January 2012
Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius Cell, Vol. 161, Issue 4 https://doi.org/10.1016/j.cell.2015.04.011	journal	May 2015
Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor gene in mice Hein, Lutz; Barsh, Gregory S.; Pratt, Richard E. Nature, Vol. 377, Issue 6551 https://doi.org/10.1038/377744a0	journal	October 1995
Allosteric sodium in class A GPCR signaling Katritch, Vsevolod; Fenalti, Gustavo; Abola, Enrique E. Trends in Biochemical Sciences, Vol. 39, Issue 5 https://doi.org/10.1016/j.tibs.2014.03.002	journal	May 2014
EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial Rice, Andrew S. C.; Dworkin, Robert H.; McCarthy, Tom D. The Lancet, Vol. 383, Issue 9929 https://doi.org/10.1016/S0140-6736(13)62337-5	journal	May 2014
Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor Ichiki, Toshihiro; Labosky, Patricia A.; Shiota, Chiyo Nature, Vol. 377, Issue 6551 https://doi.org/10.1038/377748a0	journal	October 1995
Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography Weierstall, Uwe; James, Daniel; Wang, Chong Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4309	journal	February 2014
Flexible protein–ligand docking by global energy optimization in internal coordinates Totrov, Maxim; Abagyan, Ruben Proteins: Structure, Function, and Genetics, Vol. 29, Issue S1 https://doi.org/10.1002/(SICI)1097-0134(1997)1+<215::AID-PROT29>3.0.CO;2-Q	journal	January 1997
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Molecular dynamics with coupling to an external bath Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F. The Journal of Chemical Physics, Vol. 81, Issue 8 https://doi.org/10.1063/1.448118	journal	October 1984
Crystal structure of the β2 adrenergic receptor–Gs protein complex Rasmussen, Søren G. F.; DeVree, Brian T.; Zou, Yaozhong Nature, Vol. 477, Issue 7366 https://doi.org/10.1038/nature10361	journal	July 2011
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone ϕ, ψ and Side-Chain χ ₁ and χ ₂ Dihedral Angles Best, Robert B.; Zhu, Xiao; Shim, Jihyun Journal of Chemical Theory and Computation, Vol. 8, Issue 9 https://doi.org/10.1021/ct300400x	journal	August 2012
Interaction of angiotensin II with the angiotensin type 2 receptor inhibits the cardiac transient outward potassium current Caballero, R. Cardiovascular Research, Vol. 62, Issue 1 https://doi.org/10.1016/j.cardiores.2003.12.029	journal	April 2004
Small Molecule Angiotensin II Type 2 Receptor (AT ₂ R) Antagonists as Novel Analgesics for Neuropathic Pain: Comparative Pharmacokinetics, Radioligand Binding, and Efficacy in Rats Smith, Maree T.; Wyse, Bruce D.; Edwards, Stephen R. Pain Medicine, Vol. 14, Issue 5 https://doi.org/10.1111/pme.12063	journal	May 2013
The design, binding affinity prediction and synthesis of macrocyclic angiotensin II AT1 and AT2 receptor antagonists de Laszlo, Stephen E.; Glinka, Tomasz W.; Greenlee, William J. Bioorganic & Medicinal Chemistry Letters, Vol. 6, Issue 8 https://doi.org/10.1016/0960-894X(96)00116-3	journal	April 1996
CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field Lee, Jumin; Cheng, Xi; Swails, Jason M. Journal of Chemical Theory and Computation, Vol. 12, Issue 1 https://doi.org/10.1021/acs.jctc.5b00935	journal	December 2015
From the First Selective Non-Peptide AT ₂ Receptor Agonist to Structurally Related Antagonists Murugaiah, A. M. S.; Wu, Xiongyu; Wallinder, Charlotta Journal of Medicinal Chemistry, Vol. 55, Issue 5 https://doi.org/10.1021/jm2015099	journal	February 2012
Structural Basis for Ligand Recognition and Functional Selectivity at Angiotensin Receptor Zhang, Haitao; Unal, Hamiyet; Desnoyer, Russell Journal of Biological Chemistry, Vol. 290, Issue 49 https://doi.org/10.1074/jbc.M115.689000	journal	September 2015
Potential energy functions Halgren, Thomas A. Current Opinion in Structural Biology, Vol. 5, Issue 2 https://doi.org/10.1016/0959-440X(95)80077-8	journal	April 1995
Design, Synthesis, and Biological Evaluation of the First Selective Nonpeptide AT ₂ Receptor Agonist Wan, Yiqian; Wallinder, Charlotta; Plouffe, Bianca Journal of Medicinal Chemistry, Vol. 47, Issue 24 https://doi.org/10.1021/jm049715t	journal	November 2004
Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography Liu, Wei; Ishchenko, Andrii; Cherezov, Vadim Nature Protocols, Vol. 9, Issue 9 https://doi.org/10.1038/nprot.2014.141	journal	August 2014
Systemic Infusion of Angiotensin II into Normal Rats Activates Nuclear Factor-κB and AP-1 in the Kidney Ruiz-Ortega, Marta; Lorenzo, Óscar; Rupérez, Mónica The American Journal of Pathology, Vol. 158, Issue 5 https://doi.org/10.1016/S0002-9440(10)64130-2	journal	May 2001
International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli Karnik, Sadashiva S.; Unal, Hamiyet; Kemp, Jacqueline R. Pharmacological Reviews, Vol. 67, Issue 4 https://doi.org/10.1124/pr.114.010454	journal	August 2015
Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor–Mediated Cardiomyocyte Autophagy Porrello, Enzo R.; D'Amore, Angelo; Curl, Claire L. Hypertension, Vol. 53, Issue 6 https://doi.org/10.1161/HYPERTENSIONAHA.108.128488	journal	June 2009
Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation Zhao, Yi; Foryst-Ludwig, Anna; Bruemmer, Dennis Journal of Neurochemistry, Vol. 94, Issue 5 https://doi.org/10.1111/j.1471-4159.2005.03275.x	journal	September 2005
Angiotensin II type 2 receptor (AT ₂ R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons : AT Anand, U.; Facer, P.; Yiangou, Y. European Journal of Pain, Vol. 17, Issue 7 https://doi.org/10.1002/j.1532-2149.2012.00269.x	journal	December 2012
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Rational identification and characterisation of peptide ligands for targeting polysialic acid Shastry, Divya G.; Irudayanathan, Flaviyan Jerome; Williams, Asher Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-64088-z	journal	May 2020
Potential Energy Functions Burkowski, Forbes J. Computational and Visualization Techniques for Structural Bioinformatics Using Chimera https://doi.org/10.1201/b17306-11	book	July 2014
Structural Features for Functional Selectivity at Serotonin Receptors V., Cherezov,; V., Katritch,; E., Xu, H. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/pynr-p256	text	January 2013
Allosteric sodium in class A GPCR signaling Vsevolod, Katritch,; Vadim, Cherezov,; C., Stevens, Raymond The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/5vt2-kp93	text	January 2014
EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial Rice, Andrew S. C.; Dworkin, Robert H.; McCarthy, Tom D. The Lancet, Vol. 383, Issue 9929, 1637-1647 https://doi.org/10.3410/f.718270683.793501691	journal	May 2014
Angiotensin II: from blood pressure to pain control Finnerup, Nanna Brix; Baastrup, Cathrine The Lancet, Vol. 383, Issue 9929 https://doi.org/10.1016/s0140-6736(13)62638-0	journal	May 2014
Analgesic efficacy of small-molecule angiotensin II type 2 receptor antagonists in a rat model of antiretroviral toxic polyneuropathy Smith, Maree T.; Lau, Tanya; Wallace, Victoria C. J. Behavioural Pharmacology, Vol. 25, Issue 2 https://doi.org/10.1097/fbp.0000000000000025	journal	January 2014
AT ₂ Receptor-Mediated Relaxation Is Preserved After Long-Term AT ₁ Receptor Blockade Widdop, Robert E.; Matrougui, Khalid; Levy, Bernard I. Hypertension, Vol. 40, Issue 4 https://doi.org/10.1161/01.hyp.0000033224.99806.8a	journal	October 2002
AT ₂ Receptor Activation Induces Natriuresis and Lowers Blood Pressure Kemp, Brandon A.; Howell, Nancy L.; Gildea, John J. Circulation Research, Vol. 115, Issue 3 https://doi.org/10.1161/circresaha.115.304110	journal	July 2014
Angiotensin Receptors and Autophagy Steckelings, U. Muscha; Unger, Thomas Hypertension, Vol. 53, Issue 6 https://doi.org/10.1161/hypertensionaha.109.131425	journal	June 2009

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The Renin-Angiotensin-Aldosterone System as a Therapeutic Target in Late Injury Caused by Ischemia-Reperfusion Rodríguez-Lara, Simón Quetzalcóatl; García-Benavides, Leonel; Miranda-Díaz, Alejandra Guillermina International Journal of Endocrinology, Vol. 2018 https://doi.org/10.1155/2018/3614303	journal	April 2018
Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney Patel, Sanket N.; Ali, Quaisar; Samuel, Preethi Hypertension, Vol. 70, Issue 4 https://doi.org/10.1161/hypertensionaha.117.09679	journal	October 2017
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Better agonist for the opioid receptors Badshah, Syed Lal; Ullah, Asad; Al-showiman, Salim S. Chemistry Central Journal, Vol. 12, Issue 1 https://doi.org/10.1186/s13065-018-0383-8	journal	February 2018
The association between angiotensin II type 1 receptor A1166C gene polymorphism and the risk of essential hypertension: a meta-analysis Fajar, Jonny Karunia; Susanti, Melly; Pikir, Budi Susetio Egyptian Journal of Medical Human Genetics, Vol. 20, Issue 1 https://doi.org/10.1186/s43042-019-0016-3	journal	September 2019
Short-wavelength free-electron laser sources and science: a review Seddon, E. A.; Clarke, J. A.; Dunning, D. J. Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-00596	text	January 2017
Molecular Docking and Dynamics Simulation Studies Predict Munc18b as a Target of Mycolactone: A Plausible Mechanism for Granule Exocytosis Impairment in Buruli Ulcer Pathogenesis Kwofie, Samuel; Dankwa, Bismark; Enninful, Kweku Toxins, Vol. 11, Issue 3 https://doi.org/10.3390/toxins11030181	journal	March 2019
Could Mycolactone Inspire New Potent Analgesics? Perspectives and Pitfalls Reynaert, Marie-Line; Dupoiron, Denis; Yeramian, Edouard Toxins, Vol. 11, Issue 9 https://doi.org/10.3390/toxins11090516	journal	September 2019
X-ray free electron laser: opportunities for drug discovery Cheng, Robert K. Y.; Abela, Rafael; Hennig, Michael Essays in Biochemistry, Vol. 61, Issue 5 https://doi.org/10.1042/ebc20170031	journal	November 2017
Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors Gusach, Anastasiia; Luginina, Aleksandra; Marin, Egor RWTH Aachen University https://doi.org/10.18154/rwth-2020-00731	text	January 2019
Structure-based mechanism of cysteinyl leukotriene receptor inhibition by antiasthmatic drugs Luginina, Aleksandra; Gusach, Anastasiia; Marin, Egor RWTH Aachen University https://doi.org/10.18154/rwth-2020-02115	text	January 2019
Short-wavelength free-electron laser sources and science: a review Seddon, E. A.; Clarke, J. A.; Dunning, D. J. Reports on Progress in Physics, Vol. 80, Issue 11 https://doi.org/10.1088/1361-6633/aa7cca	journal	October 2017
Angiotensin peptide synthesis and cyclic nucleotide modulation in sympathetic stellate ganglia Bardsley, Emma N.; Neely, Oliver C.; Paterson, David J. Journal of Molecular and Cellular Cardiology, Vol. 138 https://doi.org/10.1016/j.yjmcc.2019.11.157	journal	January 2020
Deciphering collaborative sidechain motions in proteins during molecular dynamics simulations Taddese, Bruck; Garnier, Antoine; Abdi, Hervé Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-72766-1	journal	September 2020
DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy Zhang, Min-Yu; Guo, Fei-Fei; Wu, Hong-Wei Oncotarget, Vol. 8, Issue 61 https://doi.org/10.18632/oncotarget.21900	journal	October 2017
In Silico Studies Targeting G-protein Coupled Receptors for Drug Research Against Parkinson’s Disease Lemos, Agostinho; Melo, Rita; Preto, Antonio Jose Current Neuropharmacology, Vol. 16, Issue 6 https://doi.org/10.2174/1570159x16666180308161642	journal	June 2018
A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel Toxins, Vol. 9, Issue 7 https://doi.org/10.3390/toxins9070227	journal	July 2017

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