Article: Interactions of Leptospiral PI-PLC with the membrane phosphoinositides: an insight of the protein-phospholipid association in the pathogenesis Journal: International Journal of Computational Biology and Drug Design (IJCBDD) 2020 Vol.13 No.2 pp.200 - 208 Abstract: Protein-phospholipid interactions encompass the basis of many biological processes, including host-pathogen interaction and disease progression. This study reports the interactions of Leptospiral PI-PLC (LA_1375) with PIP2 and PIP3. Molecular docking analysis was carried out to unveil the interactions of the protein with the plasma membrane phosphoinositides. The binding affinities of the interactions, most favourable protein-phospholipid binding poses, and the binding site residues were revealed. The binding energies were found to be -14.04 and -11.64 kcal/mol respectively for PIP2 and PIP3 interaction. Also, the analysis explored the high-affinity binding of the protein with the substrate PIP2. PIP2 is the precursor of intracellular second messengers DAG and IP3; responsible for the activation of pro-inflammatory mediators and other signalling events. Moreover, both PIP2 and PIP3 have been implicated in various cellular processes through the activation of lipid signalling cascades. Hence, further in-vitro confirmation of the annotated interactions may open up new dimensions in the pathogenesis of Leptospirosis. Inderscience Publishers - linking academia, business and industry through research

Title: Interactions of Leptospiral PI-PLC with the membrane phosphoinositides: an insight of the protein-phospholipid association in the pathogenesis

Authors: T.H. Samaha

Addresses: Regional Medical Research Centre (Indian Council of Medical Research), WHO Collaborating Centre for Diagnosis, Reference, Research and Training in Leptospirosis, Port Blair – 744103, Andaman and Nicobar Islands, India

Abstract: Protein-phospholipid interactions encompass the basis of many biological processes, including host-pathogen interaction and disease progression. This study reports the interactions of Leptospiral PI-PLC (LA_1375) with PIP2 and PIP3. Molecular docking analysis was carried out to unveil the interactions of the protein with the plasma membrane phosphoinositides. The binding affinities of the interactions, most favourable protein-phospholipid binding poses, and the binding site residues were revealed. The binding energies were found to be -14.04 and -11.64 kcal/mol respectively for PIP2 and PIP3 interaction. Also, the analysis explored the high-affinity binding of the protein with the substrate PIP2. PIP2 is the precursor of intracellular second messengers DAG and IP3; responsible for the activation of pro-inflammatory mediators and other signalling events. Moreover, both PIP2 and PIP3 have been implicated in various cellular processes through the activation of lipid signalling cascades. Hence, further in-vitro confirmation of the annotated interactions may open up new dimensions in the pathogenesis of Leptospirosis.

Keywords: Leptospirosis; phosphatidylinositol-specific phospholipase C; LA_1375; molecular docking; membrane phosphoinositides; pathogenesis.

DOI: 10.1504/IJCBDD.2020.10029440

International Journal of Computational Biology and Drug Design, 2020 Vol.13 No.2, pp.200 - 208

Received: 23 Nov 2018
Accepted: 18 May 2019
Published online: 13 May 2020 *

Full-text access for editors Access for subscribers Purchase this article Comment on this article

Title: Interactions of Leptospiral PI-PLC with the membrane phosphoinositides: an insight of the protein-phospholipid association in the pathogenesis

Keep up-to-date