Molecular modelling of the oxytocin receptor-bioligand interactions

• Autorzy: Politowska E. , Czaplewski C. , Ciarkowski J.
• Języki publikacji: EN

Abstrakty

EN

Oxytocin is a nonapeptide hormone (CYIQNCPLG-NH2, OT), controlling labor and lactation in mammalian females, via interactions with specific cellular membrane receptors (OTRs). The native hormone is cyclized via a 1-6 disulfide and its receptor belongs to the GTP-binding (G) protein-coupled receptor (GPCR) family, also known as heptahelical transmembrane (7TM) or serpentine receptors. Using a technique combining multiple sequence alignments with available experimental constraints, a reliable OTR model was built. Subsequently, the OTR complexes with a selective agonist [Thr4,Gly7]OT, a selective cyclohexapeptide antagonist L-366,948 and oxytocin itself were modeled and relaxed using a constrained simulated annealing (CSA) protocol. All three ligands seem to prefer similar modes of binding to the receptor, manifested by repeating receptor residues which directly interact with the ligands. Those involved in the three complexes are putative helices: TM3: R113, K116, Q119, M123; TM4: Q171, and TM5: I201 and T205. Most of them are the equivalent residues/positions to those found in our earlier studies, regarding related vasopressin V2 receptor/bioligand interactions.

Słowa kluczowe

EN

mammal; receptor-bioligand interaction; lactation; interaction; oxytocin; cell membrane receptor; female; hormone; molecular dynamics

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1999
• Tom: 46
• Numer: 3
• Opis fizyczny: p.581-590,fig.

Twórcy

autor

Politowska E.

• University of Gdansk, J.Sobieskiego 18, 80-952 Gdansk, Poland

autor

Czaplewski C.

autor

Ciarkowski J.

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