Engineering Dynamic Surface Peptide Networks on Butyrylcholinesterase_G117H for Enhanced Organophosphosphorus Anticholinesterase Catalysis.

ABSTRACT: The single residue mutation of butyrylcholinesterase (BChE_G117H) hydrolyzes a number of organophosphosphorus (OP) anticholinesterases. Whereas other BChE active site/proximal mutations have been investigated, none are sufficiently active to be prophylactically useful. In a fundamentally different computer simulations driven strategy, we identified a surface peptide loop (residues 278-285) exhibiting dynamic motions during catalysis and modified it via residue insertions. We evaluated these loop mutants using computer simulations, substrate kinetics, resistance to inhibition, and enzyme reactivation assays using both the choline ester and OP substrates. A slight but significant increase in reactivation was noted with paraoxon with one of the mutants, and changes in K_M

SUBMITTER: Hester KP 

PROVIDER: S-EPMC7251593 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature