Docking studies for melatonin receptors

ABSTRACT

Introduction: Melatonin is a neurohormone that controls many relevant physiological processes beyond the control of circadian rhythms. Melatonin’s actions are carried out by two main types of melatonin receptors; MT₁ and MT₂. These receptors are important, and not just because of the biological actions of its natural agonist; but also, because melatonin analogues can improve or antagonize their biological effect.

Area covered: The following article describes the importance of melatonin as a biologically relevant molecule. It also defines the receptors for this substance, as well as the second messengers coupled to these receptors. Lastly, the article describes the amino acid residues involved in the docking process in both MT₁ and MT₂ melatonin receptors.

Expert opinion: The biological actions of melatonin and their interpretations are becoming more relevant and therefore require the development of new pharmacological tools. Understanding the second messenger mechanisms involved in melatonin actions, as well as the characteristics of the docking of this molecule to MT₁ and MT₂ melatonin receptors, will permit the development of more selective agonists and antagonists which will help us to better understand this molecule as well to develop new therapeutic compounds.

KEYWORDS:

• Docking
• indoleamine
• melatonin
• neurohormone
• second messengers

Article highlights

• Melatonin is a natural compound involved in many physiological processes.

• Its actions are mediated by membrane receptors termed MT₁ and MT₂ melatonin receptors.

• MT₁ receptor’s docking of melatonin involves residues Ser110, Ser114, Phe196, His195, Trp251 and Tyr281.

• MT₂ docking involves among other aminoacids Asn175, Thr191, His208 and Tyr298.

• Apart from docking analysis, functional studies are needed to confirm which residues are really relevant for melatonin binding.

Acknowledgments

We thank Penny Rollinson for her help in the preparation of this manuscript.

Declaration of interest

HA Alkozi is a fellowship holder from the Saudi Arabian government via the Ministry of Higher Education (ref.1815). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was supported by grants from Ministerio Economia y Competitividad [SAF2013-44416-R] and [SAF2016-77084R], and Ministerio de sanidad, servicios sociales e igualdad (RETICS) [RD12/0034/0003] and [RD16/0008/0017].