Glutamine Synthetase Drugability beyond Its Active Site: Exploring Oligomerization Interfaces and Pockets.

ABSTRACT:

Background

Glutamine synthetase (GS) is a crucial enzyme to the nitrogen cycle with great commercial and pharmaceutical value. Current inhibitors target the active site, affecting GS activity indiscriminately in all organisms. As the active site is located at the interface between two monomers, the protein-protein interface (PPI) of GSs gains a new role, by providing new targets for enzyme inhibition. Exploring GSs PPI could allow for the development of inhibitors selective for specific organisms. Here we map the PPI of three GSs-human (hsGS), maize (zmGS) and Mycobacterium tuberculosis (mtGS)-and unravel new drugable pockets.

Methods

The PPI binding free energy coming from key residues on three GSs from different organisms were mapped by computational alanine scan mutagenes

SUBMITTER: Moreira C 

PROVIDER: S-EPMC6274088 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature