The Structure of the Adenosine Receptors: Implications for Drug Discovery

J. Robert Lane, Veli-Pekka Jaakola, Adriaan P IJzerman

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

Abstract

Extracellular adenosine mediates most of its physiological effects via an interaction with four G protein-coupled receptors (GPCRs), the adenosine receptors (ARs). These ARs are important pharmacological targets in the treatment of a wide variety of diseases from central nervous system disorders to ischemic injury. As for other GPCRs, drug development for the ARs has been hampered by the lack of structural data for this class of membrane proteins. However, in the past 3 years, this situation has changed with the elucidation of structures for the turkey β1-adrenoceptor, the human β2-adrenoceptor, squid rhodopsin, the activated form of bovine (rhod)opsin, the human adenosine A2A receptor, and most recently the CXCR4 chemokine receptor. In this review, the structural features of the human adenosine A2A receptor will be discussed with a particular focus on the ligand binding site. Further, the implications of this structural information for AR ligand selectivity, drug screening, homology modeling, and virtual ligand screening will be discussed.

Original languageEnglish
Title of host publicationAdvances in Pharmacology
Subtitle of host publicationPharmacology of Purine and Pyrimidine Receptors
EditorsKenneth A Jacobson, Joel Linden
Place of PublicationAmsterdam The Netherlands
PublisherElsevier
Chapter1
Pages1-40
Number of pages40
Volume61
ISBN (Electronic)9780123855268
DOIs
Publication statusPublished - 2011

Keywords

  • Adenosine receptors
  • Crystal structure
  • G protein-coupled receptors
  • Ligand selectivity
  • Molecular modeling
  • Virtual ligand screening

Cite this

Lane, J. R., Jaakola, V-P., & IJzerman, A. P. (2011). The Structure of the Adenosine Receptors: Implications for Drug Discovery. In K. A. Jacobson, & J. Linden (Eds.), Advances in Pharmacology: Pharmacology of Purine and Pyrimidine Receptors (Vol. 61, pp. 1-40). Amsterdam The Netherlands: Elsevier. https://doi.org/10.1016/B978-0-12-385526-8.00001-1
Lane, J. Robert ; Jaakola, Veli-Pekka ; IJzerman, Adriaan P. / The Structure of the Adenosine Receptors : Implications for Drug Discovery. Advances in Pharmacology: Pharmacology of Purine and Pyrimidine Receptors. editor / Kenneth A Jacobson ; Joel Linden. Vol. 61 Amsterdam The Netherlands : Elsevier, 2011. pp. 1-40
@inbook{67d566b8574d4ea6b7b43caf816b12a6,
title = "The Structure of the Adenosine Receptors: Implications for Drug Discovery",
abstract = "Extracellular adenosine mediates most of its physiological effects via an interaction with four G protein-coupled receptors (GPCRs), the adenosine receptors (ARs). These ARs are important pharmacological targets in the treatment of a wide variety of diseases from central nervous system disorders to ischemic injury. As for other GPCRs, drug development for the ARs has been hampered by the lack of structural data for this class of membrane proteins. However, in the past 3 years, this situation has changed with the elucidation of structures for the turkey β1-adrenoceptor, the human β2-adrenoceptor, squid rhodopsin, the activated form of bovine (rhod)opsin, the human adenosine A2A receptor, and most recently the CXCR4 chemokine receptor. In this review, the structural features of the human adenosine A2A receptor will be discussed with a particular focus on the ligand binding site. Further, the implications of this structural information for AR ligand selectivity, drug screening, homology modeling, and virtual ligand screening will be discussed.",
keywords = "Adenosine receptors, Crystal structure, G protein-coupled receptors, Ligand selectivity, Molecular modeling, Virtual ligand screening",
author = "Lane, {J. Robert} and Veli-Pekka Jaakola and IJzerman, {Adriaan P}",
year = "2011",
doi = "10.1016/B978-0-12-385526-8.00001-1",
language = "English",
volume = "61",
pages = "1--40",
editor = "Jacobson, {Kenneth A} and Linden, {Joel }",
booktitle = "Advances in Pharmacology",
publisher = "Elsevier",
address = "Netherlands",

}

Lane, JR, Jaakola, V-P & IJzerman, AP 2011, The Structure of the Adenosine Receptors: Implications for Drug Discovery. in KA Jacobson & J Linden (eds), Advances in Pharmacology: Pharmacology of Purine and Pyrimidine Receptors. vol. 61, Elsevier, Amsterdam The Netherlands, pp. 1-40. https://doi.org/10.1016/B978-0-12-385526-8.00001-1

The Structure of the Adenosine Receptors : Implications for Drug Discovery. / Lane, J. Robert; Jaakola, Veli-Pekka; IJzerman, Adriaan P.

Advances in Pharmacology: Pharmacology of Purine and Pyrimidine Receptors. ed. / Kenneth A Jacobson; Joel Linden. Vol. 61 Amsterdam The Netherlands : Elsevier, 2011. p. 1-40.

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

TY - CHAP

T1 - The Structure of the Adenosine Receptors

T2 - Implications for Drug Discovery

AU - Lane, J. Robert

AU - Jaakola, Veli-Pekka

AU - IJzerman, Adriaan P

PY - 2011

Y1 - 2011

N2 - Extracellular adenosine mediates most of its physiological effects via an interaction with four G protein-coupled receptors (GPCRs), the adenosine receptors (ARs). These ARs are important pharmacological targets in the treatment of a wide variety of diseases from central nervous system disorders to ischemic injury. As for other GPCRs, drug development for the ARs has been hampered by the lack of structural data for this class of membrane proteins. However, in the past 3 years, this situation has changed with the elucidation of structures for the turkey β1-adrenoceptor, the human β2-adrenoceptor, squid rhodopsin, the activated form of bovine (rhod)opsin, the human adenosine A2A receptor, and most recently the CXCR4 chemokine receptor. In this review, the structural features of the human adenosine A2A receptor will be discussed with a particular focus on the ligand binding site. Further, the implications of this structural information for AR ligand selectivity, drug screening, homology modeling, and virtual ligand screening will be discussed.

AB - Extracellular adenosine mediates most of its physiological effects via an interaction with four G protein-coupled receptors (GPCRs), the adenosine receptors (ARs). These ARs are important pharmacological targets in the treatment of a wide variety of diseases from central nervous system disorders to ischemic injury. As for other GPCRs, drug development for the ARs has been hampered by the lack of structural data for this class of membrane proteins. However, in the past 3 years, this situation has changed with the elucidation of structures for the turkey β1-adrenoceptor, the human β2-adrenoceptor, squid rhodopsin, the activated form of bovine (rhod)opsin, the human adenosine A2A receptor, and most recently the CXCR4 chemokine receptor. In this review, the structural features of the human adenosine A2A receptor will be discussed with a particular focus on the ligand binding site. Further, the implications of this structural information for AR ligand selectivity, drug screening, homology modeling, and virtual ligand screening will be discussed.

KW - Adenosine receptors

KW - Crystal structure

KW - G protein-coupled receptors

KW - Ligand selectivity

KW - Molecular modeling

KW - Virtual ligand screening

UR - http://www.scopus.com/inward/record.url?scp=79955948707&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-385526-8.00001-1

DO - 10.1016/B978-0-12-385526-8.00001-1

M3 - Chapter (Book)

VL - 61

SP - 1

EP - 40

BT - Advances in Pharmacology

A2 - Jacobson, Kenneth A

A2 - Linden, Joel

PB - Elsevier

CY - Amsterdam The Netherlands

ER -

Lane JR, Jaakola V-P, IJzerman AP. The Structure of the Adenosine Receptors: Implications for Drug Discovery. In Jacobson KA, Linden J, editors, Advances in Pharmacology: Pharmacology of Purine and Pyrimidine Receptors. Vol. 61. Amsterdam The Netherlands: Elsevier. 2011. p. 1-40 https://doi.org/10.1016/B978-0-12-385526-8.00001-1