PMID: 11907156Mar 22, 2002Paper

Beta(1)-selective agonist (-)-1-(3,4-dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for beta(1)-selective binding in resting and active states

The Journal of Pharmacology and Experimental Therapeutics
Yoshiyuki SugimotoH Kurose

Abstract

(-)-1-(3,4-Dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] is a highly selective beta(1)-adrenergic receptor (beta(1)AR) agonist. To study the binding site of beta(1)-selective agonist, chimeric beta(1)/beta(2)ARs and Ala-substituted beta(1)ARs were constructed. Several key residues of beta(1)AR [Leu(110) and Thr(117) in transmembrane domain (TMD) 2], and Phe(359) in TMD 7] were found to be responsible for beta(1)-selective binding of (-)-RO363, as determined by competitive binding. Based on these results, we built a three-dimensional model of the binding domain for (-)-RO363. The model indicated that TMD 2 and TMD 7 of beta(1)AR form a binding pocket; the methoxyphenyl group of N-substituent of (-)-RO363 seems to locate within the cavity surrounded by Leu(110), Thr(117), and Phe(359). The amino acids Leu(110) and Phe(359) interact with the phenyl ring of (-)-RO363, whereas Thr(117) forms hydrogen bond with the methoxy group of (-)-RO363. To examine the interaction of these residues with beta(1)AR in an active state, each of the amino acids was changed to Ala in a constitutively active (CA)-beta(1)AR mutant. The degree of decrease in the affinity of CA-beta(1)AR for (-)-RO363 was essentially the same as that of...Continue Reading

References

Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·T FrielleR J Lefkowitz
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·C D StraderR A Dixon
Dec 1, 1994·Protein Science : a Publication of the Protein Society·R TanimuraH Nakamura
Jan 1, 1994·Annual Review of Biochemistry·C D StraderR A Dixon
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·K WielandM J Lohse
Oct 11, 1996·The Journal of Biological Chemistry·S Acharya, S S Karnik
Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·A ScheerS Cotecchia
Jul 11, 1998·The Journal of Biological Chemistry·U Gether, B K Kobilka
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·N G Abdulaev, K D Ridge
Sep 3, 1999·FEBS Letters·A LattionS Cotecchia

❮ Previous
Next ❯

Citations

Jul 3, 2008·Nature·Tony WarneGebhard F X Schertler
Sep 15, 2011·PloS One·Angel GonzálezXavier Deupi
Jul 17, 2014·Biophysical Journal·Supriyo Bhattacharya, Nagarajan Vaidehi
May 25, 2004·Molecular Pharmacology·Dezhong YinCraig C Malbon
May 22, 2009·Nature·Daniel M RosenbaumBrian K Kobilka
Oct 24, 2018·Journal of Medicinal Chemistry·Márton VassChris de Graaf
Jun 9, 2006·Journal of Medicinal Chemistry·Linda A Rezmann-VittiSimon N S Louis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.

© 2022 Meta ULC. All rights reserved