Yeast Cyclophilin A Protein As A Model For Aging Studies
Researchers:
Institute for Research in Molecular Medicine, USM
Dr. Eugene Ong Boon Beng
School of Biological Sciences, USM
Prof. Dr. Mohammed Razip Samian
RIKEN
Dr. Hiroyuki Osada
Dr. Nobumoto Watanabe
Summary:
Ageing is a biological process involving many proteins and biochemical pathways. Among the many proteins involved, one particular ubiquitous group known as Cyclophilins (CyPs), have been the centre of attraction. It is a family of proteins that are evolutionarily well conserved and present in all prokaryotes and eukaryotes. Peptidyl-prolyl cis-trans isomerase A (also known as Cyclophilin A (CyPA) or Cyclosporin A-binding protein) is an ubiquitously distributed protein belonging to the immunophilin family (1). The CyPA protein is highly conserved and can be found in yeast Saccharomyces cerevisiae, roundworm Caenorhabditis elegans, fruitfly Drosophila melanogaster and humans (UniProt IDs: P14832, P52009, P25007 and P62937). CyPA has enzymatic activity that regulates protein folding and trafficking in the cell. Initially, CyPA was thought to only function intracellularly but recent studies showed that it can be secreted by cells in response to inflammatory stimuli.
In this study, we will approach the study of the yeast Cyclophilin A (CPR1) in silico and in vivo. In parallel, we will pursue virtual screening of the inhibitors of CPR1 (PDB ID: 1IST) and whole cell-based assay to screen for inhibitors of CPR1 from local Malaysian plant extracts and small molecule libraries such as the RIKEN NPDepo (2). Known inhibitors of CPR1 such as cyclosporin A will also be used as controls or as bioprobes to characterize the molecular interactions. The well-characterized genome of yeast that can be easily manipulated and the facility of yeast cells to high-throughput platforms make S. cerevisiae a leading model organism for studying pathways relevant to human ageing and diseases.
References
- Nigro, P, Pompilio, G & Capogrossi, MC (2013). Cyclophilin A: a key player for human disease. Cell Death Dis, 4, e888.
- Tomiki, T, Saito, T, Ueki, M, Konno, H, Asaoka, T, Suzuki, R, Uramoto, M, Kakeya, H & Osada, H (2006). RIKEN Natural Products Encyclopedia (RIKEN NPEdia), a Chemical Database of RIKEN Natural Products Depository (RIKEN NPDepo). J Comp Aid Chem, 7, 157-162.