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Volume 10, Issue 8 (Suppl) J Proteomics Bioinform, an open access journal
ISSN: 0974-276X Structural Biology 2017
September 18-20, 2017
9th International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
Structural mechanism of partial agonists and antagonists of PPARgamma for use as antidiabetics
John B Bruning1, Ted Kamenecka2 and Pat Griffin2
1The University of Adelaide, Australia
2The Scripps Research Institute, USA
Synthetic full agonists of Peroxisome proliferator-activated receptor gamma (PPARγ) have been prescribed for the treatment
of diabetes due to their ability to regulate glucose homeostasis and insulin sensitization. While the use of full agonists
of PPARγ has been hampered due to severe side effects, partial agonists and antagonists have shown promise due to their
decreased incidence of such side effects in preclinical models. No kinetic information has been forthcoming in regard to the
mechanism of full versus partial agonism of PPARγ to date and little structural and dynamic information is available which
can shed light on the mechanistic difference between full and partial agonists as well as antagonists. We have used X-ray
crystallography, cellular assays, Hydrogen Deuterium Exchange (HDX), and Surface Plasmon Resonance (SPR) to probe the
mechanism of several PPARγ partial agonists and antagonists. Our findings demonstrate that not only do partial agonists and
antagonists act through distinct transcriptional mechanisms, they also demonstrate differences in structure, dynamics, and
kinetics as compared to full agonists.
Biography
John B Bruning completed BSc from Texas A&M University in 1997. He began crystallography in the Laboratory of Yousif Shamoo at Rice University. He worked
on the structural mechanism of the human sliding clamp and its interactions with DNA replication proteins. He received PhD in 2005 and completed 2 successful
Post-docs. The first was at the Scripps Research Institute from 2005-2007 working on structural studies of nuclear receptors including PPAR, RXR, ER, and TR;
second Post-Doc was with Jim Sacchettini in the Houston Medical centre. He was a part of the TB structural genomics consortium. He received his first faculty
position at the University of Adelaide in 2012 as a Lecturer. He was tenured in 2015 and promoted to Senior Lecturer in 2016. He was also appointed Adjunct
Professor of the Scripps Research Institute in 2016.
John B Bruning et al., J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100