Protein Conformational Dynamics Underlie Selective Recognition of Thermophilic over Mesophilic Enzyme I by a Substrate Analogue.

ABSTRACT: Substrate selectivity is an important preventive measure to decrease the possibility of cross interactions between enzymes and metabolites that share structural similarities. In addition, understanding the mechanisms that determine selectivity towards a particular substrate increases the knowledge base for designing specific inhibitors for target enzymes. Here, we combine NMR, molecular dynamics (MD) simulations, and protein engineering to investigate how two substrate analogues, allylicphosphonate (cPEP) and sulfoenolpyruvate (SEP), recognize the mesophilic (eEIC) and thermophilic (tEIC) homologues of the receptor domain of bacterial Enzyme I, which has been proposed as a target for antimicrobial research. Chemical Shift Perturbation (CSP) experiments show that cPEP and SEP recognize tEIC

SUBMITTER: Singh A 

PROVIDER: S-EPMC9856155 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature