Search for content and authors
 

Crystal structure of β-adrenergic receptor as a new template in homology modeling of GPCR. Application to serotonin 5-HT1A and 5-HT7 receptors

Elżbieta Pieniążek 1Mateusz Nowak 1Andrzej J. Bojarski 1Małgorzata Jarończyk 2Zdzisław Chilmonczyk 2

1. Polish Academy of Sciences. Institute of Pharmacology, Smętna 12, Kraków 31-343, Poland
2. National Medicines Institute (NIL), Chełmska 30/34, Warszawa 00-725, Poland

Abstract

When dificulties in receiving crystal structures appear, homology modeling aproach is the best way to obtain three dimensional structure of a protein. Procedure is realtively simple, but results depend on degree of similarity between a target and a template sequence. Since 2000 there was one available crystal structure of transmembrane domain of GPCR protein: the bovine rhodopsin. We, and others have previously shown that regardless of relatively low sequence identity, it was possible to obtain useful rhodopsin based models of serotonin receptors, such as 5-HT1A and 5HT7. In October 2007, a high resolution structure of another GPCR, beta-2 adrenergic receptor, was solved. Very close evolutionary relationships between 5-HT receptors and beta adrenoreceptors give us possibility to improve comparative models of serotonin receptors and to verify our previous results. New homology models will be used in a process of drug design and virtual screening.

Acknowledgement
This study was partly supported by the Network "Synthesis, structure and therapeutic properties of compounds and organic substances" coordinated by the Institute of Organic Chemistry Polish Academy of Sciences.

 

Legal notice
  • Legal notice:
 

Related papers

Presentation: Poster at VI Multidyscyplinarna Konferencja Nauki o Leku, by Elżbieta Pieniążek
See On-line Journal of VI Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2008-03-14 16:37
Revised:   2009-06-07 00:48