Structural Analysis of MurG Interactions with Substrates, Inhibitors, and MraY

Citation

Brackney, Helen Maya (2024) Structural Analysis of MurG Interactions with Substrates, Inhibitors, and MraY. Senior thesis (Major), California Institute of Technology. doi:10.7907/y324-9f36. https://resolver.caltech.edu/CaltechTHESIS:10242023-173046393

Abstract

The peptidoglycan layer in bacterial cells is a popular target for antibiotic development. The membrane protein MraY and peripheral membrane protein MurG are part of critical steps in the synthesis of peptidoglycan. Lipid I, a lipid precursor formed by MraY, is recognized by MurG through its soluble domain. Currently, there is no structure of MurG with bound Lipid I, and the residues required for this interaction have not been conclusively defined. Crystallographic methods and Cryo-Electron Microscopy were applied to study the interactions between MurG and the soluble domain of Lipid I by binding Park’s Nucleotide, Lipid II, or a Lipid I analog were used to study the interactions of MurG and MraY with the aforementioned substrates. By adding Park’s Nucleotide, Murgocil, Lipid II, the Lipid I analog, or a combination of the listed additives to concentrated MurG, crystals formed under optimized conditions. We aim to obtain electron-density maps from these techniques to model the structure of MurG.

Thesis Files