Abstract
We performed total alanine scanning mutational analysis (ASMA) of the residues lining the ligand binding pocket (LBP) of the human vitamin D receptor (hVDR) to investigate allosteric effects of ligands in the function of nuclear receptors (NRs). This was accomplished for the first time in the NR superfamily. The effects of ligand structure were also examined in this system (termed 2D-ASMA) using 8 representative VDR ligands. The results clearly revealed the role and importance of all amino acid residues lining the LBP and the relationships between ligand binding and transcriptional potency. 2D-ASMA indicated ligand-specific ligand-protein interactions, which are essential in determining the transactivation potency of the ligand. Taking the results as a whole, we suggest a ligand-mediated allosteric network, which allows transmission of information from ligands to the interfaces of the VDR in association with protein cofactors and was shown to be linked to a part of the network identified by statistical coupling analysis (SCA).
Keywords: ligand binding pocket (LBP), conformation, VDR agonists, 19-Norvitamin D Analogs, R391A
Current Topics in Medicinal Chemistry
Title: Ligand Recognition by Vitamin D Receptor: Total Alanine Scanning Mutational Analysis of the Residues Lining the Ligand Binding Pocket of Vitamin D Receptor
Volume: 6 Issue: 12
Author(s): Sachiko Yamada and Keiko Yamamoto
Affiliation:
Keywords: ligand binding pocket (LBP), conformation, VDR agonists, 19-Norvitamin D Analogs, R391A
Abstract: We performed total alanine scanning mutational analysis (ASMA) of the residues lining the ligand binding pocket (LBP) of the human vitamin D receptor (hVDR) to investigate allosteric effects of ligands in the function of nuclear receptors (NRs). This was accomplished for the first time in the NR superfamily. The effects of ligand structure were also examined in this system (termed 2D-ASMA) using 8 representative VDR ligands. The results clearly revealed the role and importance of all amino acid residues lining the LBP and the relationships between ligand binding and transcriptional potency. 2D-ASMA indicated ligand-specific ligand-protein interactions, which are essential in determining the transactivation potency of the ligand. Taking the results as a whole, we suggest a ligand-mediated allosteric network, which allows transmission of information from ligands to the interfaces of the VDR in association with protein cofactors and was shown to be linked to a part of the network identified by statistical coupling analysis (SCA).
Export Options
About this article
Cite this article as:
Yamada Sachiko and Yamamoto Keiko, Ligand Recognition by Vitamin D Receptor: Total Alanine Scanning Mutational Analysis of the Residues Lining the Ligand Binding Pocket of Vitamin D Receptor, Current Topics in Medicinal Chemistry 2006; 6 (12) . https://dx.doi.org/10.2174/156802606777864881
DOI https://dx.doi.org/10.2174/156802606777864881 |
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
-
Predictive In Silico Studies of Human 5-hydroxytryptamine Receptor Subtype 2B (5-HT2B) and Valvular Heart Disease
Current Topics in Medicinal Chemistry Derivatives of 6-Nitrobenzimidazole Inhibit Fructose-Mediated Protein Glycation and Intracellular Reactive Oxygen Species Production
Medicinal Chemistry Metabolic Regulation and Behavior: How Hunger Produces Arousal - An Insect Study
Endocrine, Metabolic & Immune Disorders - Drug Targets Helicobacter pylori Interference with Micronutrients and Orally AdministeredDrugs:ANewMechanism Explaining its Role in Extragastric Disorders
Mini-Reviews in Medicinal Chemistry In Vitro Drug Permeation Enhancement Potential of Aloe Gel Materials
Current Drug Delivery Neuro-Transmitters in the Central Nervous System & their Implication in Learning and Memory Processes
Current Medicinal Chemistry Bis(2-aminoimidazolines) and Bisguanidines: Synthetic Approaches, Antiparasitic Activity and DNA Binding Properties
Current Medicinal Chemistry B-Type Natriuretic Peptide for Diagnosis and Therapy
Recent Patents on Cardiovascular Drug Discovery The Influence of Gender and Menopausal Status on Hba1c Variation in a Big Data Study of a Saudi Population
Current Diabetes Reviews Vascular Wall Responses to Angioplasty and Stenting: Endothelial Injury, Neointimal Hyperplasia and the Process of Restenosis
Vascular Disease Prevention (Discontinued) The sdLDL Reduces MRC1 Expression Level and Secretion of Histamin e in Differentiated M2-macrophages from Patients with Coronary Artery Stenosis
Cardiovascular & Hematological Disorders-Drug Targets Circulating Endothelial Progenitor Cells as Biomarkers for Prediction of Cardiovascular Outcomes
Current Medicinal Chemistry The Role of Neuropeptides and Neurohormones in Neurogenic Cardiac Arrhythmias
Current Drug Targets - Cardiovascular & Hematological Disorders The Battle of the Sexes for Stroke Therapy: Female- Versus Male-Derived Stem Cells
CNS & Neurological Disorders - Drug Targets Role of Statins in Diabetes Complications
Current Diabetes Reviews Non-pharmacological Strategies Against Systemic Inflammation: Molecular Basis and Clinical Evidence
Current Pharmaceutical Design Cancer Chemoprevention by Targeting the Epigenome
Current Drug Targets Caveolin-3: Its Importance in Muscle Function and Pathology
Current Genomics Vascular Endothelial Growth Factor (VEGF) in the Pathogenesis of Diabetic Nephropathy of Type 1 Diabetes Mellitus
Current Drug Targets Acknowledgements to Contributors:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery