Abstract
The development of ligands for the A3 adenosine receptor (AR) has been directed mainly by traditional medicinal chemistry, but the influence of structure-based approaches is increasing. Rhodopsin-based homology modeling had been used for many years to obtain three-dimensional models of the A3AR, and different A3AR models have been published describing the hypothetical interactions with known A3AR ligands having different chemical scaffolds. The recently published structure of the human A2AAR provides a new template for GPCR modeling, however even use of the A2AAR as a template for modeling other AR subtypes is still imprecise. The models compared here are based on bovine rhodopsin, the human β2-adrenergic receptor, and the A2AAR as templates. The sequence of the human A3AR contains only one cysteine residue (Cys166) in the second extracellular loop (EL2), which putatively forms a conserved disulfide bridge with the respective cysteine residues of TM3 (Cys83). Homology models of the A3AR have been helpful in providing structural hypotheses for the design of new ligands. Site-directed mutagenesis of the A3AR shows an important role in ligand recognition for specific residues in TM3, TM6 and TM7.
Current Pharmaceutical Design
Title: Human A3 Adenosine Receptor as Versatile G Protein-Coupled Receptor Example to Validate the Receptor Homology Modeling Technology
Volume: 15 Issue: 35
Author(s): Erika Morizzo, Stephanie Federico, Giampiero Spalluto and Stefano Moro
Affiliation:
Abstract: The development of ligands for the A3 adenosine receptor (AR) has been directed mainly by traditional medicinal chemistry, but the influence of structure-based approaches is increasing. Rhodopsin-based homology modeling had been used for many years to obtain three-dimensional models of the A3AR, and different A3AR models have been published describing the hypothetical interactions with known A3AR ligands having different chemical scaffolds. The recently published structure of the human A2AAR provides a new template for GPCR modeling, however even use of the A2AAR as a template for modeling other AR subtypes is still imprecise. The models compared here are based on bovine rhodopsin, the human β2-adrenergic receptor, and the A2AAR as templates. The sequence of the human A3AR contains only one cysteine residue (Cys166) in the second extracellular loop (EL2), which putatively forms a conserved disulfide bridge with the respective cysteine residues of TM3 (Cys83). Homology models of the A3AR have been helpful in providing structural hypotheses for the design of new ligands. Site-directed mutagenesis of the A3AR shows an important role in ligand recognition for specific residues in TM3, TM6 and TM7.
Export Options
About this article
Cite this article as:
Morizzo Erika, Federico Stephanie, Spalluto Giampiero and Moro Stefano, Human A3 Adenosine Receptor as Versatile G Protein-Coupled Receptor Example to Validate the Receptor Homology Modeling Technology, Current Pharmaceutical Design 2009; 15 (35) . https://dx.doi.org/10.2174/138161209789824777
DOI https://dx.doi.org/10.2174/138161209789824777 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Synthesis, Anticonvulsant and Antimicrobial Activities of Some New [1-(2-Naphthyl)-2-(pyrazol-1-yl)ethanone]oxime Ethers
Medicinal Chemistry Editorial [ Targeting G Protein-Coupled 7TM Receptors in Inflammation Guest Editor: Dr. Trond Ulven ]
Current Topics in Medicinal Chemistry Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?
Current Drug Targets Tools For Decision-Making In Older Cancer Patients. Role Of The Comprehensive Geriatric Assessment
Anti-Cancer Agents in Medicinal Chemistry The Role of Oxytocin in Neuropsychiatric Disorders
Current Medicinal Chemistry Serotonin (5-HT) in the Regulation of Depression-Related Emotionality: Insight from 5-HT Transporter and Tryptophan Hydroxylase-2 Knockout Mouse Models
Current Drug Targets Embryonic Stem Cells or Induced Pluripotent Stem Cells? A DNA Integrity Perspective
Current Gene Therapy Role of Environmental Factors in Cocaine Addiction
Current Pharmaceutical Design Neurogenesis and Alzheimers Disease: Biology and Pathophysiology in Mice and Men
Current Alzheimer Research Association between <i>Toxoplasma gondii</i> Infection and Headache: A Systematic Review and Meta-Analysis
Infectious Disorders - Drug Targets Diversity and Variability of the Effects of Nicotine on Different Cortical Regions of the Brain. Therapeutic and Toxicological Implications
Central Nervous System Agents in Medicinal Chemistry The Etiology of Hypertension in the Metabolic Syndrome Part Four: The Systemic Perspective – The Role of the Neuroendocrine and Immune Systems,and the Challenge of Integration
Current Vascular Pharmacology Meet Our Editorial Board Member
Current Alzheimer Research Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets Preoperative Levosimendan. A New Way for Organoprotection
Current Pharmaceutical Design Invasive and Non-Invasive Electrical Neuromodulation in Trigeminal Nerve Neuralgia: A Systematic Review and Meta-Analysis
Current Neuropharmacology The Toxic Conformation of the 42-residue Amyloid β Peptide and Its Relevance to Oxidative Stress in Alzheimers Disease
Mini-Reviews in Medicinal Chemistry The Role of the Tyrosine Kinase Inhibitor STI571 in the Treatment of Cancer
Current Cancer Drug Targets 10 Years of SELDI: What Have we Learnt?
Current Proteomics Pharmacogenetics of Phase I and Phase II Drug Metabolism
Current Pharmaceutical Design