A role of salt bridges in mediating drug potency: A lesson from the N-myristoyltransferase inhibitors.

ABSTRACT: The salt bridge is the strongest non-covalent interaction in nature and is known to participate in protein folding, protein-protein interactions, and molecular recognition. However, the role of salt bridges in the context of drug design has remained not well understood. Here, we report that a common feature in the mechanism of inhibition of the N-myristoyltransferases (NMT), promising targets for the treatment of protozoan infections and cancer, is the formation of a salt bridge between a positively charged chemical group of the small molecule and the negatively charged C-terminus of the enzyme. Substituting the inhibitor positively charged amine group with a neutral methylene group prevents the formation of the salt bridge and leads to a dramatic activity loss. Molecular dynamics simulati

SUBMITTER: Spassov DS 

PROVIDER: S-EPMC9871453 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature