Poster Presentation The 44th Lorne Conference on Protein Structure and Function 2019

Development of binding and activity assays for phosphatidylcholine-specific phospholipase C (#134)

Nabangshu Sharma 1 , Ivanhoe Leung 1 , David Barker 1 , Johannes Reynisson 1 , Euphemia Leung 2 , Christopher Squire 3
  1. School of Chemical Sciences, University of Auckland, City Campus, AUCKLAND, New Zealand
  2. Auckland Cancer Society Research Centre and Department of Molecular Medicine and Pathology, University of Auckland, Grafton, AUCKLAND, New Zealand
  3. School of Biological Sciences, University of Auckland, City Campus, AUCKLAND, New Zealand

Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyses the hydrolysis of phosphatidylcholine (PC), which is a phospholipid, into phosphocholine and diacylglycerol (Figure 1). PC-PLC has emerged as a novel target for the development of new anti-cancer drugs, as enhanced PC-PLC activity was observed during tumour progression. Interestingly, however, the identity of mammalian PC-PLC is not known to date. By using PC-PLC from Bacillus cereus (PC-PLCBc) as a model system, we report our progress in the development of new PC-PLC inhibitiors by using a combined structural and biophysical-based approach. We hope our study will enable the development of new anti-cancer agents, as well as facilitating our quest to identify mammalian PC-PLC (e.g. as chemical probe).

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Figure.1: PC-PLC catalyses the conversion of phosphatidylcholine to phosphocholine and diaglycerol.