Utilizing in silico and in vitro methods to identify possible binding sites of a novel ligand against Pseudomonas aeruginosa phospholipase toxin ExoU

Krista Chamberlain; Mya Johnson; Terry-Elinor Reid; Tzvia I Springer

doi:10.1016/j.bbrep.2021.101188

Utilizing in silico and in vitro methods to identify possible binding sites of a novel ligand against Pseudomonas aeruginosa phospholipase toxin ExoU

Biochem Biophys Rep. 2021 Dec 16:29:101188. doi: 10.1016/j.bbrep.2021.101188. eCollection 2022 Mar.

Authors

Krista Chamberlain¹, Mya Johnson², Terry-Elinor Reid¹, Tzvia I Springer¹

Affiliations

¹ Pharmaceutical Sciences Department, School of Pharmacy, Concordia University Wisconsin, Mequon, WI, 53097, USA.
² Harvard Faculty of Arts and Science, School of Engineering and Applied Sciences, 150 Western Ave, Boston, MA, 02134, USA.

Abstract

Multi-drug resistant infections caused by the opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa), are a continuing problem that contribute to morbidity and mortality in immunocompromised hosts such as cystic fibrosis (CF), wound and burn patients. The bacterial toxin ExoU is one of four potent toxins that P. aeruginosa secretes into the epithelial cells of hosts. In this study, NMR Saturation Transfer Difference (STD) and in silico Schrödinger Computational Modeling were used to identify a possible binding site of a novel ligand methoctramine targeting ExoU. Future project goals will be to design a structure activity relationship (SAR) study of methoctramine and ExoU and lead to a new drug solving ExoU toxicity P. aeruginosa exerts in the clinical environment.

Keywords: DPFGSE, Double Pulsed Field Gradient Spin Echo; E. coli, Escherichia coli; ExoU; MES, Molecular Electrostatic Potential; NMR, Nuclear Magnetic Resonance; P. aeruginosa, Pseudomonas aeruginosa; Phospholipase; Pseudomonas aeruginosa; STD, Saturation Transfer Difference; Saturation transfer nuclear magnetic resonance.