-transparent.png){kind=logo}
Insights into PPARγ Phosphorylation and Its Inhibition Mechanism. 2020
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Via Salaria km. 29.300, 00015 Monterotondo Stazione, Rome, Italy.
PPARγ represents a key target for the treatment of type 2 diabetes and metabolic syndrome. Synthetic antidiabetic drugs activating PPARγ are accompanied by serious undesirable side effects related to their agonism. In the search for new PPARγ regulators, inhibitors of PPARγ phosphorylation on S245 mediated by CDK5 represent an opportunity for the development of an improved generation of antidiabetic drugs acting through this nuclear receptor. We have employed a multidisciplinary approach, including protein-protein docking, X-ray crystallography, NMR, HDX, MD simulations, and site-directed mutagenesis to investigate conformational changes in PPARγ that impair the ability of CDK5 to interact with PPARγ and hence inhibit PPARγ phosphorylation. Finally, we describe an alternative inhibition mechanism adopted by a ligand bound far from the phosphorylation site.
Related Publications
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
December 2016,
Archives of biochemistry and biophysics,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
June 2020,
The Journal of biological chemistry,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
June 2022,
Nature structural & molecular biology,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
January 2010,
Biopolymers,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
April 2020,
International journal of molecular sciences,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
April 1994,
Chromosoma,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
December 2017,
ACS chemical neuroscience,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
May 2021,
Molecules (Basel, Switzerland),
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
August 2000,
Protein science : a publication of the Protein Society,
Roberta Montanari, and
Davide Capelli, and
Keiko Yamamoto, and
Hirono Awaishima, and
Kimina Nishikata, and
Arjan Barendregt, and
Albert J R Heck, and
Fulvio Loiodice, and
Fabio Altieri, and
Alessandro Paiardini, and
Alessandro Grottesi, and
Luciano Pirone, and
Emilia Pedone, and
Franck Peiretti, and
Jean Michel Brunel, and
Toshimasa Itoh, and
Giorgio Pochetti
September 2019,
Journal of structural biology,
