دورية أكاديمية
Exploring the mechanism of PPARγ phosphorylation mediated by CDK5.
| العنوان: | Exploring the mechanism of PPARγ phosphorylation mediated by CDK5. |
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| المؤلفون: | Ribeiro Filho HV; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil; Graduate Program in Biosciences and Technology of Bioactive Products, Institute of Biology, State University of Campinas (Unicamp), Campinas, SP, Brazil., Guerra JV; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil; Graduate Program in Biosciences and Technology of Bioactive Products, Institute of Biology, State University of Campinas (Unicamp), Campinas, SP, Brazil., Cagliari R; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil; Graduate Program in Biosciences and Technology of Bioactive Products, Institute of Biology, State University of Campinas (Unicamp), Campinas, SP, Brazil., Batista FAH; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil., Le Maire A; Centre de Biochimie Structurale CNRS, Université de Montpellier, Montpellier, France., Oliveira PSL; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil; Graduate Program in Biosciences and Technology of Bioactive Products, Institute of Biology, State University of Campinas (Unicamp), Campinas, SP, Brazil., Figueira ACM; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil; Graduate Program in Biosciences and Technology of Bioactive Products, Institute of Biology, State University of Campinas (Unicamp), Campinas, SP, Brazil. Electronic address: ana.figueira@lnbio.cnpem.br. |
| المصدر: | Journal of structural biology [J Struct Biol] 2019 Sep 01; Vol. 207 (3), pp. 317-326. Date of Electronic Publication: 2019 Jul 15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 9011206 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-8657 (Electronic) Linking ISSN: 10478477 NLM ISO Abbreviation: J Struct Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Diego : Academic Press, c1990- |
| مواضيع طبية MeSH: | Protein Conformation*, Cyclin-Dependent Kinase 5/*chemistry , Multiprotein Complexes/*chemistry , PPAR gamma/*chemistry, Animals ; Binding Sites/genetics ; Cyclin-Dependent Kinase 5/genetics ; Cyclin-Dependent Kinase 5/metabolism ; Humans ; Ligands ; Models, Molecular ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Mutation ; PPAR gamma/genetics ; PPAR gamma/metabolism ; Phosphorylation ; Protein Binding |
| مستخلص: | Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor with a key role in metabolic processes and is target of CDK5 kinase phosphorylation at S245 (S273 in PPARγ isoform 2), thereby inducing insulin resistance. A remarkable effort has been addressed to find PPARγ ligands that inhibit S245 phosphorylation, but the poor understanding in this field challenges the design of such ligands. Here, through computational and biophysical methods, we explored an experimentally validated model of PPARγ-CDK5 complex, and we presented K261, K263 or K265, which are conserved in mammals, as important anchor residues for this interaction. In addition, we observed, from structural data analysis, that PPARγ ligands that inhibit S245 phosphorylation are not in direct contact with these residues; but induce structural modifications in PPARγ:CDK5/p25 interface. In summary, our PPARγ and CDK5/p25 interaction analyses open new possibilities for the rational design of novel inhibitors that impair S245 phosphorylation. (Copyright © 2019 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Cyclin-dependent kinase 5; Non-contiguous phosphorylation site; PPARγ ligands; PPARγ phosphorylation; PPARγ:CDK5/p25 docking model |
| المشرفين على المادة: | 0 (Ligands) 0 (Multiprotein Complexes) 0 (PPAR gamma) EC 2.7.11.1 (Cyclin-Dependent Kinase 5) EC 2.7.11.22 (CDK5 protein, human) |
| تواريخ الأحداث: | Date Created: 20190719 Date Completed: 20200608 Latest Revision: 20200608 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.jsb.2019.07.007 |
| PMID: | 31319193 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1095-8657 |
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| DOI: | 10.1016/j.jsb.2019.07.007 |