دورية أكاديمية
Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ.
| العنوان: | Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ. |
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| المؤلفون: | Pham B; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, United States., Cheng Z; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, United States., Lopez D; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, United States., Lindsay RJ; UT-ORNL Graduate School of Genome Science and Technology, Knoxville, TN, United States., Foutch D; UT-ORNL Graduate School of Genome Science and Technology, Knoxville, TN, United States., Majors RT; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, United States., Shen T; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, United States. |
| المصدر: | Frontiers in molecular biosciences [Front Mol Biosci] 2022 Jun 15; Vol. 9, pp. 904445. Date of Electronic Publication: 2022 Jun 15 (Print Publication: 2022). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101653173 Publication Model: eCollection Cited Medium: Print ISSN: 2296-889X (Print) Linking ISSN: 2296889X NLM ISO Abbreviation: Front Mol Biosci Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Media S.A., [2014]- |
| مستخلص: | The receptor RORγ belongs to the nuclear receptor superfamily that senses small signaling molecules and regulates at the gene transcription level. Since RORγ has a high basal activity and plays an important role in immune responses, inhibitors targeting this receptor have been a focus for many studies. The receptor-ligand interaction is complex, and often subtle differences in ligand structure can determine its role as an inverse agonist or an agonist. We examined more than 130 existing RORγ crystal structures that have the same receptor complexed with different ligands. We reported the features of receptor-ligand interaction patterns and the differences between agonist and inverse agonist binding. Specific changes in the contact interaction map are identified to distinguish active and inactive conformations. Further statistical analysis of the contact interaction patterns using principal component analysis reveals a dominant mode which separates allosteric binding vs. canonical binding and a second mode which may indicate active vs. inactive structures. We also studied the nature of constitutive activity by performing a 100-ns computer simulation of apo RORγ. Using constitutively active nuclear receptor CAR as a comparison, we identified a group of conserved contacts that have similar contact strength between the two receptors. These conserved contact interactions, especially a couple key contacts in H11-H12 interaction, can be considered essential to the constitutive activity of RORγ. These protein-ligand and internal protein contact interactions can be useful in the development of new drugs that direct receptor activity. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Pham, Cheng, Lopez, Lindsay, Foutch, Majors and Shen.) |
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| فهرسة مساهمة: | Keywords: constitutive activity; inverse agonist; nuclear receptor; protein-ligand interaction; statistical analysis |
| تواريخ الأحداث: | Date Created: 20220705 Latest Revision: 20220716 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC9240913 |
| DOI: | 10.3389/fmolb.2022.904445 |
| PMID: | 35782874 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2296-889X |
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| DOI: | 10.3389/fmolb.2022.904445 |