Work

Human P2Y 6 Receptor: Molecular Modeling Leads to the Rational Design of a Novel Agonist Based on a Unique Conformational Preference

Year: 2020

Type: article

Abstract: Combining molecular dynamics (MD) in a hydrated phospholipids (DOPC) bilayer, Monte Carlo search, and synthesis of locked nucleotide analogues we discovered that the Southern conformation of the ribose is preferred for ligand recognition by the P2Y6 receptor. 2′-Deoxy-(S)-methanocarbaUDP was found to be a full agonist of the receptor and displayed a 10-fold higher potency than the corresponding flexible 2′-deoxyUDP. MD results also suggested a conformational change of the second extracellular loop consequent to agonist binding.

Source: Carolina Digital Repository (University of North Carolina at Chapel Hill)

DOI: 10.17615/c3bm-j883

Authors: Harden, T. Kendall, Jacobson, Kenneth A., Marquez, Victor E., Joshi, Bhalchandra V., Mamedova, Liaman, Costanzi, Stefano, Gonzalez-Moa, Maria J., Maddileti, Savitri

Language: English

Topic: Adenosine and Purinergic Signaling

Subfield: Physiology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

OpenAlex ID: W4298864411

FWCI: 0.157

Cites:

Cited by: 2

Related to: 10