Abstract
The large superfamily of nuclear receptors is a family of ligand-activated transcription factors involved in numerous fundamental processes and shows many common characteristics and behaviors. The comprehension of these roles is of fundamental importance to select the right target for receptor structure-based screening. Recently, during the last ten years, several crystallographic structures of nuclear receptors complexed with ligands have been registered in the Protein Data Bank, supplying a structural basis for computational simulations. The macroscopic flexibility of helix12 and local flexibility of some amino acids sidechains within cavities of the Ligand Binding Domain suggest a reason for the behavior of these receptors toward different ligands. Several approaches have been applied in trying to explain this flexibility and to predict how ligand binding can influence complex conformations. In this short review, we present an introduction to the structure and function of nuclear receptors, specifically the estrogen, androgen, glucorticoid, peroxisome proliferator, steroid, thyroid and vitamin D receptors, and a discussion of the state-of-the-art of induced fit approaches for the nuclear receptor family.
Keywords: Nuclear Receptor Superfamily, Ligand Binding Domain, Micro- and macroscopic flexibility, Allosteric effect, closed-agonistic conformation, open antagonistic conformation, Helix H12 positioning, amino acids, helix12, androgen, glucorticoid, thyroid, vitamin D receptors, NRs, vitamin D, retinoids, eicosanoids, A-F, AD, TFIIF, RAP74, GR, DBD, NLS, LBD, X-ray crystallography, LBP, PR, ER, AR, TR, VDR, RAR, PPAR, EERs, NOR1, RXR, HRE, Allosteric Effects, BMS614, NcoR1, HDACs, PXR, DHT, MD, Met895, CPA, WT, LIE analysis, QSAR, Glucocorticoid Receptor, Raloxifene, Cyproterone acetate, Aldosterone, Progesterone, MF, IFD, NALLRYLLD, Cys798
Current Topics in Medicinal Chemistry
Title: Induced Fit Simulations on Nuclear Receptors
Volume: 11 Issue: 2
Author(s): Monika Nocker and Pietro Cozzini
Affiliation:
Keywords: Nuclear Receptor Superfamily, Ligand Binding Domain, Micro- and macroscopic flexibility, Allosteric effect, closed-agonistic conformation, open antagonistic conformation, Helix H12 positioning, amino acids, helix12, androgen, glucorticoid, thyroid, vitamin D receptors, NRs, vitamin D, retinoids, eicosanoids, A-F, AD, TFIIF, RAP74, GR, DBD, NLS, LBD, X-ray crystallography, LBP, PR, ER, AR, TR, VDR, RAR, PPAR, EERs, NOR1, RXR, HRE, Allosteric Effects, BMS614, NcoR1, HDACs, PXR, DHT, MD, Met895, CPA, WT, LIE analysis, QSAR, Glucocorticoid Receptor, Raloxifene, Cyproterone acetate, Aldosterone, Progesterone, MF, IFD, NALLRYLLD, Cys798
Abstract: The large superfamily of nuclear receptors is a family of ligand-activated transcription factors involved in numerous fundamental processes and shows many common characteristics and behaviors. The comprehension of these roles is of fundamental importance to select the right target for receptor structure-based screening. Recently, during the last ten years, several crystallographic structures of nuclear receptors complexed with ligands have been registered in the Protein Data Bank, supplying a structural basis for computational simulations. The macroscopic flexibility of helix12 and local flexibility of some amino acids sidechains within cavities of the Ligand Binding Domain suggest a reason for the behavior of these receptors toward different ligands. Several approaches have been applied in trying to explain this flexibility and to predict how ligand binding can influence complex conformations. In this short review, we present an introduction to the structure and function of nuclear receptors, specifically the estrogen, androgen, glucorticoid, peroxisome proliferator, steroid, thyroid and vitamin D receptors, and a discussion of the state-of-the-art of induced fit approaches for the nuclear receptor family.
Export Options
About this article
Cite this article as:
Nocker Monika and Cozzini Pietro, Induced Fit Simulations on Nuclear Receptors, Current Topics in Medicinal Chemistry 2011; 11 (2) . https://dx.doi.org/10.2174/156802611794863526
DOI https://dx.doi.org/10.2174/156802611794863526 |
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
-
Meet Our Editor
Current Metabolomics Scaling Down SAGE: from miniSAGE to microSAGE
Current Pharmaceutical Biotechnology Osteoblast Differentiation and Control by Vitamin D and Vitamin D Metabolites
Current Pharmaceutical Design New Developments in Anti-Angiogenic Therapy of Cancer, Review and Update
Anti-Cancer Agents in Medicinal Chemistry Marine Metabolites Overcoming or Circumventing Multidrug Resistance Mediated by ATP-Dependent Transporters: A New Hope for Patient with Tumors Resistant to Conventional Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Dimethylaminoparthenolide, A Water Soluble Parthenolide, Suppresses Lung Tumorigenesis Through Down-Regulating the STAT3 Signaling Pathway
Current Cancer Drug Targets Cytochrome P450 Retinoic Acid 4-Hydroxylase Inhibitors: Potential Agents for Cancer Therapy
Mini-Reviews in Medicinal Chemistry Fertility Preservation in Women After the Cancer
Current Pharmaceutical Design Gold(III) Complexes in the Oncological Preclinical Arena: From Aminoderivatives to Peptidomimetics
Current Topics in Medicinal Chemistry Osteoimmunology and Beyond
Current Medicinal Chemistry Recent Developments on Thiourea Based Anticancer Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Preclinical and Clinical Studies of Chidamide (CS055/HBI-8000), An Orally Available Subtype-selective HDAC Inhibitor for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Chalcones as Promising Lead Compounds on Cancer Therapy
Current Medicinal Chemistry Phosphoproteomics as a Promising Tool for Broadening the Analysis of Clinical Samples and for the Fight Against Cancer Disease
Current Pharmaceutical Analysis CDK Inhibitors Induce Mitochondria-mediated Apoptosis Through the Activation of Polyamine Catabolic Pathway in LNCaP, DU145 and PC3 Prostate Cancer Cells
Current Pharmaceutical Design DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer
Current Cancer Drug Targets The Impact of the Theory-Based Training on Beliefs of Women towards Breast Cancer Screening Behaviors
Current Women`s Health Reviews Functional Genomics Approaches in Cancer Research
Current Genomics Calcium Carbonate Microparticles as Carriers of <sup>224</sup>Ra: Impact of Specific Activity in Mice with Intraperitoneal Ovarian Cancer
Current Radiopharmaceuticals PET and SPECT Imaging of Tumor Biology: New Approaches Towards Oncology Drug Discovery and Development
Current Computer-Aided Drug Design