Understanding the molecular basis of agonist/antagonist mechanism of GPER1/GPR30 through structural and energetic analyses

The Journal of Steroid Biochemistry and Molecular Biology
D Méndez-LunaJosé Correa-Basurto

Abstract

The G-protein coupled receptors (GPCRs) represent the largest superfamily of membrane proteins in charge to pass the cell signaling after binding with their cognate ligands to the cell interior. In breast cancer, a GPCR named GPER1 plays a key role in the process of growth and the proliferation of cancer cells. In a previous study, theoretical methods were applied to construct a model of GPER1, which later was submitted to molecular dynamics (MD) simulations to perform a docking calculation. Based on this preceding work, it is known that GPER1 is sensitive to structural differences in its binding site. However, due to the nature of that past study, conformational changes linked to the ligand binding were not observed. Therefore, in this study, in order to explore the conformational changes coupled to the agonist/antagonist binding, MD simulations of about 0.25μs were performed for the free and bound states, summarizing 0.75μs of MD simulation in total. For the bound states, one agonist (G-1) and antagonist (G-15) were chosen since is widely known that these two molecules cause an impact on GPER1 mobility. Based on the conformational ensemble generated through MD simulations, we found that despite G-1 and G-15 being stabilized b...Continue Reading

References

Dec 1, 1993·Proteins·A AmadeiH J Berendsen
Oct 24, 2003·Molecular Pharmacology·Derek N RobertsonRory Mitchell
Feb 12, 2004·Science's STKE : Signal Transduction Knowledge Environment·Tanja KortemmeDavid Baker
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Feb 12, 2005·Science·Chetana M RevankarEric R Prossnitz
Aug 30, 2005·Trends in Endocrinology and Metabolism : TEM·Edward J Filardo, Peter Thomas
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Jan 7, 2006·Bioinformatics·Mikhail A LomizeHenry I Mosberg
Mar 8, 2006·Nature Chemical Biology·Cristian G BologaEric R Prossnitz
Sep 2, 2006·Endocrinology·K MoriartyJ R Bender
Sep 29, 2006·Journal of Medicinal Chemistry·Gregory L WarrenMartha S Head
Dec 29, 2006·Molecular Pharmacology·G Enrico RovatiRichard R Neubig
Feb 12, 2008·Trends in Pharmacological Sciences·Eric R ProssnitzJeffrey B Arterburn
May 12, 2009·Nature Chemical Biology·Megan K DennisEric R Prossnitz
May 26, 2009·Molecular and Cellular Endocrinology·Eric R Prossnitz, Marcello Maggiolini
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Xiao Jie YaoBrian Kobilka
Dec 24, 2009·Current Pharmaceutical Design·Irina G Tikhonova, Stefano Costanzi
Mar 26, 2010·Journal of Computational Chemistry·Maarten G WolfGerrit Groenhof
Oct 14, 2010·Physiology·Xavier Deupi, Brian K Kobilka
Jun 1, 2011·Nucleic Acids Research·Aurélien GrosdidierOlivier Michielin
Jul 26, 2011·The Journal of Steroid Biochemistry and Molecular Biology·Megan K DennisEric R Prossnitz
Feb 4, 2012·Current Medicinal Chemistry·B TrzaskowskiS Filipek
Apr 14, 2012·Biophysical Chemistry·Martiniano BelloEnrique García-Hernández
Feb 5, 2013·Cell·Rie NygaardBrian K Kobilka
May 7, 2013·Expert Opinion on Drug Discovery·Martiniano BelloJosé Correa-Basurto
Jun 4, 2013·Journal of Theoretical Biology·Sunil Kumar TripathiSanjeev Kumar Singh
Dec 18, 2013·Biophysical Chemistry·Ferran FeixasJ Andrew McCammon
Jan 1, 2014·Obstetrics and Gynecology International·Whitney K PetrieEric R Prossnitz

❮ Previous
Next ❯

Citations

Dec 6, 2018·International Journal of Molecular Sciences·Rosamaria LappanoMarcello Maggiolini
Nov 20, 2018·Anti-cancer Agents in Medicinal Chemistry·Oscar J Zacarías-LaraJosé Correa-Basurto
Jan 17, 2019·International Journal of Molecular Sciences·Li-Han HsuShu-Huei Kao
Aug 28, 2020·Frontiers in Endocrinology·Fedora GrandeBruno Rizzuti
Jul 31, 2021·The Science of the Total Environment·Xiuchang LiuAiqian Zhang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.