Pyruvate dehydrogenase kinase 4 (PDK4) could be involved in a regulatory role in apoptosis and a link between apoptosis and insulin resistance

Experimental and Molecular Pathology
Zodwa DlaminiLungile Shoba-Zikhali

Abstract

Pyruvate dehydrogenase kinase 4 (PDK4), a mammalian mitochondrial serine kinase has emerged as an interesting candidate for diabetes therapy. Due to the high prevalence of this disease especially type 2 diabetes (T2D) and the health complications associated with it, there is extensive effort to find the appropriate treatment. Understanding the regulation of PDK4 activity would therefore contribute significantly to the development of therapeutic agents. This research outlines the utilization of bioinformatics tools such as Interweaver, ClustalW and Protein Structure Visualizer, in order to predict proteins that potentially interact with PDK4 and possibly regulate its activity. Interweaver database identified 96 proteins that have possible interaction sites for PDK4. Protein p100/p49, containing a death domain that is known to have a role in suppressing apoptosis, was identified as a potential partner for PDK4. The alignment between p100/p49 primary sequence and that of PDK4 using ClustalW demonstrated sequence similarity between the two proteins. Swiss PDB Viewer then located the positions of the amino acids that are in the hypothetical protein binding motif of p100/p49 within the 3D structure of hPDK4. These amino acids were fo...Continue Reading

References

Sep 1, 1992·Neuron·J Schlessinger, A Ullrich
Mar 1, 1990·Journal of Molecular Graphics·G Vriend
Dec 1, 1995·The Journal of Biological Chemistry·R GudiK M Popov
Jan 23, 1999·The Journal of Biological Chemistry·J E PessinS Okada
Mar 14, 2000·Current Opinion in Cell Biology·J P WhiteheadD E James
Jun 29, 2000·Trends in Pharmacological Sciences·C J Bailey
Aug 10, 2000·Trends in Cell Biology·S Desagher, J C Martinou
Sep 21, 2000·Pathophysiology : the Official Journal of the International Society for Pathophysiology·K Kannan, S K Jain
Oct 24, 2000·Trends in Endocrinology and Metabolism : TEM·D Accili
Feb 27, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·C A Baumann, A R Saltiel
Jul 4, 2001·Journal of Endocrinological Investigation·P Formisano, F Beguinot
Aug 3, 2001·The Journal of Biological Chemistry·C N SteussyJ A Hamilton
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
Dec 13, 2002·Current Drug Targets. Immune, Endocrine and Metabolic Disorders·M C Sugden, M J Holness
May 23, 2003·Bioinformatics·See-Kiong NgSoon-Heng Tan
Oct 14, 2003·Biochemical Pharmacology·Thomas Mandrup-Poulsen
Jan 20, 2004·Pharmacology & Therapeutics·Zodwa DlaminiMakhosazana Zungu
Apr 10, 2004·The Journal of Biological Chemistry·Alam Nur-E-KamalLeroy F Liu
Apr 16, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Margaret L ShumateRobert N Cooney
Jun 16, 2005·Diabetes Research and Clinical Practice·Maciej T Malecki
Jul 5, 2005·Biochemical and Biophysical Research Communications·Hyun Sun LeeKoanhoi Kim
Aug 9, 2005·Current Opinion in Biotechnology·Tomer Nir, Yuval Dor
Feb 21, 2007·Cellular and Molecular Life Sciences : CMLS·T E Roche, Y Hiromasa
Aug 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Frédéric TremblayAndré Marette
Oct 25, 2011·Diabetes Research and Clinical Practice·Seong-Su MoonJung-Guk Kim
Nov 15, 2011·Diabetes Research and Clinical Practice·David R WhitingJonathan Shaw
Jun 18, 2014·Diabetes Care·Jane L ChiangUNKNOWN Type 1 Diabetes Sourcebook Authors

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