Systematic analyses of the sequence conservation and ligand interaction patterns of purinergic P1 and P2Y receptors provide a structural basis for receptor selectivity.
3D structures
Clustering
Ligand selectivity
Purinergic P1 and P2Y receptor
Receptor-ligand interactions
Sequence conservation
Journal
Computational and structural biotechnology journal
ISSN: 2001-0370
Titre abrégé: Comput Struct Biotechnol J
Pays: Netherlands
ID NLM: 101585369
Informations de publication
Date de publication:
2023
2023
Historique:
received:
21
11
2022
revised:
09
01
2023
accepted:
09
01
2023
entrez:
26
1
2023
pubmed:
27
1
2023
medline:
27
1
2023
Statut:
epublish
Résumé
Purinergic receptors are membrane proteins that regulate numerous cellular functions by catalyzing reactions involving purine nucleotides or nucleosides. Among the three receptor families, i.e., P1, P2X, and P2Y, the P1 and P2Y receptors share common structural features of class A GPCR. Comprehensive sequence and structural analysis revealed that the P1 and P2Y receptors belong to two distinct groups. They exhibit different ligand-binding site features that can distinguish between specific activators. These specific amino acid residues in the binding cavity may be involved in the selectivity and unique pharmacological behavior of each subtype. In this study, we conducted a structure-based analysis of purinergic P1 and P2Y receptors to identify their evolutionary signature and obtain structural insights into ligand recognition and selectivity. The structural features of the P1 and P2Y receptor classes were compared based on sequence conservation and ligand interaction patterns. Orthologous protein sequences were collected for the P1 and P2Y receptors, and sequence conservation was calculated based on Shannon entropy to identify highly conserved residues. To analyze the ligand interaction patterns, we performed docking studies on the P1 and P2Y receptors using known ligand information extracted from the ChEMBL database. We analyzed how the conserved residues are related to ligand-binding sites and how the key interacting residues differ between P1 and P2Y receptors, or between agonists and antagonists. We extracted new similarities and differences between the receptor subtypes, and the results can be used for designing new ligands by predicting hotspot residues that are important for functional selectivity.
Identifiants
pubmed: 36698973
doi: 10.1016/j.csbj.2023.01.010
pii: S2001-0370(23)00012-0
pmc: PMC9860165
doi:
Types de publication
Journal Article
Langues
eng
Pagination
889-898Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing financial or other interests.
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