121
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Mechanistic insights into sodium ion-mediated ligand binding affinity and modulation of 5-HT2B GPCR activity: implications for drug discovery and development

, , & ORCID Icon
Received 26 Oct 2023, Accepted 02 Mar 2024, Published online: 26 Mar 2024

References

  • White KL, Eddy MT, Gao ZG, et al. Structural connection between activation microswitch and allosteric sodium site in GPCR signaling. Structure. 2018;26(2):259–269.e5. doi: 10.1016/j.str.2017.12.013.
  • Zou R, Wang X, Li S, et al. The role of metal ions in G protein‐coupled receptor signalling and drug discovery. Wiley Interdiscip Rev Comput Mol Sci. 2022;12(2):e1565.
  • Vickery ON, Carvalheda CA, Zaidi SA, et al. Intracellular transfer of Na + in an active-state G-protein-coupled receptor. Structure. 2018;26(1):171–180.e2. doi: 10.1016/j.str.2017.11.013.
  • Jaakola V, Griffith MT, Hanson MA, et al. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science. 2008;322(5905):1211–1217. doi: 10.1126/science.1164772.
  • Palczewski K, Kumasaka T, Hori T, et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science. 2000;289(5480):739–745. doi: 10.1126/science.289.5480.739.
  • Weis WI, Kobilka BK. The molecular basis of G protein–coupled receptor activation. Annu Rev Biochem. 2018;87(1):897–919. doi: 10.1146/annurev-biochem-060614-033910.
  • Granier S, Kim S, Fung JJ, et al. FRET-based measurement of GPCR conformational changes. Methods Mol Biol. 2009;552:253–268.
  • Hoffmann C, Zürn A, Bünemann M, et al. Conformational changes in G-protein-coupled receptors – the quest for functionally selective conformations is open. Br J Pharmacol. 2008;153(Suppl 1):358–366.
  • van der Westhuizen ET, Valant C, Sexton PM, et al. Endogenous allosteric modulators of G protein-coupled receptors. J Pharmacol Exp Ther. 2015;353(2):246–260. doi: 10.1124/jpet.114.221606.
  • McCorvy JD, Roth BL. Structure and function of serotonin G protein coupled receptors. Pharmacol Ther. 2015;150:129–142. doi: 10.1016/j.pharmthera.2015.01.009.
  • Yuan S, Filipek S, Palczewski K, et al. Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway. Nat Commun. 2014;5(1):4733. doi: 10.1038/ncomms5733.
  • Pert CB, Pasternak G, Snyder SH. Opiate agonists and antagonists discriminated by receptor binding in brain. Science. 1973;182(4119):1359–1361. doi: 10.1126/science.182.4119.1359.
  • Tsai BS, Lefkowitz RJ. Agonist-specific effects of monovalent and divalent cations on adenylate cyclase-coupled alpha adrenergic receptors in rabbit platelets. Mol Pharmacol. 1978;14(4):540–548.
  • Pert CB, Snyder SH. Opiate receptor binding of agonists and antagonists affected differentially by sodium. Mol Pharmacol. 1974;10(6):868–879.
  • Pasternak GW, Snowman AM, Snyder SH. Selective enhancement of [3H] opiate agonist binding by divalent cations. Mol Pharmacol. 1975;11(6):735–744.
  • Wacker D, Wang S, McCorvy JD, et al. Crystal structure of an LSD-bound human serotonin receptor. Cell. 2017;168(3):377–389.e12. doi: 10.1016/j.cell.2016.12.033.
  • Waterhouse A, Bertoni M, Bienert S, et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018;46(W1):W296–W303. doi: 10.1093/nar/gky427.
  • Wang Y, Wang Q, Huang H, et al. A crowdsourcing open platform for literature curation in UniProt. PLoS Biol. 2021;19(12):e3001464. doi: 10.1371/journal.pbio.3001464.
  • Wang Q, Zhou Y, Huang J, et al. Structure, function, and pharmaceutical ligands of 5-hydroxytryptamine 2B receptor. Pharmaceuticals. 2021;14(2):76. doi: 10.3390/ph14020076.
  • Colovos C, Yeates TO. Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci. 1993;2(9):1511–1519. doi: 10.1002/pro.5560020916.
  • Chauhan A, Sangwan N, Singh J, et al. Allosteric modulation of conserved motifs and helices in 5HT2BR: advances drug discovery and therapeutic approach towards drug resistant epilepsy. J Biomol Struct Dyn. 2023;41(22):13113–13126.
  • Chauhan A, Singh J, Sangwan N, et al. Designing the 5HT2BR structure and its modulation as a therapeutic target for repurposing approach in drug-resistant epilepsy. Epilepsy Res. 2023;194:107168. doi: 10.1016/j.eplepsyres.2023.107168.
  • Chauhan A, Singh J, Sangwan N, et al. An atomic level investigation of sodium ions regulating agonist and antagonist binding in the active site of a novel target 5HT2BR against drug-Resistant epilepsy. Cell Biochem Biophys. 2023;81(2):253–267. doi: 10.1007/s12013-023-01143-2.
  • Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Protoc Chem Biol. 2015;1263:243–250.
  • Bowers KJ, Chow DE, Xu H, et al. Scalable algorithms for molecular dynamics simulations on commodity clusters. SC'06: Proc 2006 ACM/IEEE Conf Supercomputing. 2006:43.
  • Heller H, Schaefer M, Schulten K. Molecular dynamics simulation of a bilayer of 200 lipids in the gel and in the liquid crystal phase. J Phys Chem. 1993;97(31):8343–8360. doi: 10.1021/j100133a034.
  • Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14(1):33–38. doi: 10.1016/0263-7855(96)00018-5.
  • Chan HS, Xu Y, Tan L, et al. Enhancing the signaling of GPCRs via orthosteric ions. ACS Cent Sci. 2020;6(2):274–282. doi: 10.1021/acscentsci.9b01247.
  • Silberstein SD, Hargreaves RJ. The history and pharmacology of ergotamine and dihydroergotamine. InDrug treatment of migraine and other headaches. Switzerland: Karger Publishers. 2000; Vol. 17, pp. 52–65.
  • Ramírez Rosas MB, Labruijere S, Villalón CM, et al. Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs. Expert Opin Pharmacother. 2013;14(12):1599–1610. Aug 1 doi: 10.1517/14656566.2013.806487.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.