Abstract
For a long time, there have been no experimentally determined structural data for any adenosine receptor (AR) and the only approach available for making structure/function correlations about these proteins has been homology modeling. While the early attempts to model these receptors followed the crystallization of bacteriorhodopsin, the cryomicroscopy studies of bovine and frog rhodopsin, and the modeling of a Cα-template for the TM helices in the rhodopsin family of GPCRs, the crystallization of bovine rhodopsin by Palczewski was of extreme importance as it first provided the crystal structure of an eukaryotic GPCR to be used as template for more realistic homology models. Since then, rhodopsin-based modeling became the routine approach to develop AR structural models that proved to be useful for interpretation of site-directed mutagenesis data and for molecular docking studies. The recently reported crystal structures of the adrenergic beta1 and beta2 receptors only partially confirmed the structural features showed by bovine rhodopsin, raising a question about which template would have been better for further modeling of ARs. Such question remained actually not-answered, due to the publication in late 2008 of the crystal structure of human adenosine A2A receptor (AA2AR). Since its publication, this structure has been used for ligands docking analysis and has provided a high similarity template for homology modeling of the other AR subtypes. Still, the AA2AR crystal structure allows to verify the hypotheses that were made on the basis of the previously reported homology modeling and molecular docking.
Keywords: Adenosine receptors, docking, homology modeling, molecular modeling, mutagenesis, structure-based drug design
Current Topics in Medicinal Chemistry
Title: Adenosine Receptor Modeling: What Does the A2A Crystal Structure Tell Us?
Volume: 10 Issue: 10
Author(s): D. Dal Ben, C. Lambertucci, G. Marucci, R. Volpini and G. Cristalli
Affiliation:
Keywords: Adenosine receptors, docking, homology modeling, molecular modeling, mutagenesis, structure-based drug design
Abstract: For a long time, there have been no experimentally determined structural data for any adenosine receptor (AR) and the only approach available for making structure/function correlations about these proteins has been homology modeling. While the early attempts to model these receptors followed the crystallization of bacteriorhodopsin, the cryomicroscopy studies of bovine and frog rhodopsin, and the modeling of a Cα-template for the TM helices in the rhodopsin family of GPCRs, the crystallization of bovine rhodopsin by Palczewski was of extreme importance as it first provided the crystal structure of an eukaryotic GPCR to be used as template for more realistic homology models. Since then, rhodopsin-based modeling became the routine approach to develop AR structural models that proved to be useful for interpretation of site-directed mutagenesis data and for molecular docking studies. The recently reported crystal structures of the adrenergic beta1 and beta2 receptors only partially confirmed the structural features showed by bovine rhodopsin, raising a question about which template would have been better for further modeling of ARs. Such question remained actually not-answered, due to the publication in late 2008 of the crystal structure of human adenosine A2A receptor (AA2AR). Since its publication, this structure has been used for ligands docking analysis and has provided a high similarity template for homology modeling of the other AR subtypes. Still, the AA2AR crystal structure allows to verify the hypotheses that were made on the basis of the previously reported homology modeling and molecular docking.
Export Options
About this article
Cite this article as:
Dal Ben D., Lambertucci C., Marucci G., Volpini R. and Cristalli G., Adenosine Receptor Modeling: What Does the A2A Crystal Structure Tell Us?, Current Topics in Medicinal Chemistry 2010; 10 (10) . https://dx.doi.org/10.2174/156802610791293145
DOI https://dx.doi.org/10.2174/156802610791293145 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Prostaglandin EP Receptor Subtypes Involved in Regulating HCO3- Secretion from Gastroduodenal Mucosa
Current Pharmaceutical Design Adenosine and Sleep
Current Neuropharmacology Fermented Grape Marc (FGM): Immunomodulating Properties and its Potential Exploitation in the Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Recent Advances in the Rationale Design of GPER Ligands
Current Medicinal Chemistry The Progress of Epilepsy after Stroke
Current Neuropharmacology Development and Validation of 'Level A' In Vitro - In Vivo Correlation for Extended Release Tablets of Lamotrigine
Current Bioactive Compounds Outfielders Playing in the Infield: Functions of Aging-Associated "Nuclear" Proteins in the Mitochondria
Current Molecular Medicine Editorial [Hot topic: Pharmacotherapies for Alcoholism: The Old and the New (Guest Editor: M. Foster Olive)]
CNS & Neurological Disorders - Drug Targets Amyloid-β Aggregation Inhibitory and Neuroprotective Effects of Xanthohumol and its Derivatives for Alzheimer’s Diseases
Current Alzheimer Research γ-Secretase-Regulated Signaling: Notch, APP, and Alzheimers Disease
Current Psychopharmacology Counter-Regulatory Role of Bile Acid Activated Receptors in Immunity and Inflammation
Current Molecular Medicine Gliogenesis and Glial Pathology in Depression
CNS & Neurological Disorders - Drug Targets Technological Advances in Antigen Delivery and Synthetic Peptide Vaccine Developmental Strategies
Mini-Reviews in Medicinal Chemistry The Path from Anti Parkinson Drug Selegiline and Rasagiline to Multifunctional Neuroprotective Anti Alzheimer Drugs Ladostigil and M30
Current Alzheimer Research Current and Future Issues in the Development of Spinal Agents for the Management of Pain
Current Neuropharmacology Safety and Complications Reporting Update on the Re-Implantation of Culture-Expanded Mesenchymal Stem Cells Using Autologous Platelet Lysate Technique
Current Stem Cell Research & Therapy Locked Nucleic Acid Holds Promise in the Treatment of Cancer
Current Pharmaceutical Design Altered Amplitude of Low-frequency Fluctuations in Early and Late Mild Cognitive Impairment and Alzheimer's Disease
Current Alzheimer Research Pharmacological Characteristics of Parenteral IGF-I Administration
Current Pharmaceutical Biotechnology Molecular Mechanisms Regulating Matrix Metalloproteinases
Current Topics in Medicinal Chemistry