Abstract
Nuclear receptors (NRs) are ligand-dependent transcription factors that play a central role in various physiological processes. The pharmaceutical industry has great interest in this gene-family for the discovery of novel or improved drugs for treatment of, for example, cancer, infertility, or diabetes. The usage of threedimensional coordinates of protein structures to analyse and predict interactions with ligands is an important aspect of this process. All NR ligand-binding domains have a similar fold, which allows for comparison of the structures of their three main functional sites: the ligand-binding pocket, the cofactor-binding groove, and the dimerization interface. We performed an analysis of nearly one hundred NR ligand-binding domain structures, and identified the functionally important residues. The combined knowledge about the shape of the binding sites and the residues involved in the binding is important for drug design in two ways. First, knowledge about the location of residues that interact with a ligand in all crystal structures or in certain subfamilies assists in the design and docking of drugs. Second, similarities and differences in the residue types of the most frequent ligand- and cofactor-binding residues provide insight about potential cross-reactivity of ligands or cofactors.
Keywords: nuclear receptor, ligand binding, cofactor binding, dimerization, protein structure, data mining
Current Medicinal Chemistry
Title: The Nuclear Receptor Ligand-Binding Domain: A Family-Based Structure Analysis
Volume: 12 Issue: 9
Author(s): Simon Folkertsma, Paula I. Van Noort, Ralph F.J. Brandt, Emmanuel Bettler, Gerrit Vriend and Jacob de Vlieg
Affiliation:
Keywords: nuclear receptor, ligand binding, cofactor binding, dimerization, protein structure, data mining
Abstract: Nuclear receptors (NRs) are ligand-dependent transcription factors that play a central role in various physiological processes. The pharmaceutical industry has great interest in this gene-family for the discovery of novel or improved drugs for treatment of, for example, cancer, infertility, or diabetes. The usage of threedimensional coordinates of protein structures to analyse and predict interactions with ligands is an important aspect of this process. All NR ligand-binding domains have a similar fold, which allows for comparison of the structures of their three main functional sites: the ligand-binding pocket, the cofactor-binding groove, and the dimerization interface. We performed an analysis of nearly one hundred NR ligand-binding domain structures, and identified the functionally important residues. The combined knowledge about the shape of the binding sites and the residues involved in the binding is important for drug design in two ways. First, knowledge about the location of residues that interact with a ligand in all crystal structures or in certain subfamilies assists in the design and docking of drugs. Second, similarities and differences in the residue types of the most frequent ligand- and cofactor-binding residues provide insight about potential cross-reactivity of ligands or cofactors.
Export Options
About this article
Cite this article as:
Folkertsma Simon, Noort I. Van Paula, Brandt F.J. Ralph, Bettler Emmanuel, Vriend Gerrit and Vlieg de Jacob, The Nuclear Receptor Ligand-Binding Domain: A Family-Based Structure Analysis, Current Medicinal Chemistry 2005; 12 (9) . https://dx.doi.org/10.2174/0929867053764699
DOI https://dx.doi.org/10.2174/0929867053764699 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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