Protonation State of Active-Site Histidines, Reaction Mechanism and Stereoselectivity in β-Alanine Synthase: A Computational Study.

ABSTRACT: β-Alanine synthase (βAS), which is a dizinc metalloenzyme, catalyzes the irreversible hydrolysis of N-carbamyl-β-alanine (NCβA) to β-alanine. This enzyme has potential applications for β-amino acid production. Understanding the reaction mechanism and selectivity of βAS at atomic details can help design and engineer the enzyme for cascade biocatalysis. Here, the protonation states of two conserved active-site histidine residues (His262 and His397 in Saccharomyces kluyveri) of βAS were investigated by means of combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics (MD) simulation, as well as the ONIOM QM/QM' approach. The calculations predicted that both His262 and His397 should be neutral for efficient catalysis. Furthermore, the βAS reaction mechanism

SUBMITTER: Meelua W 

PROVIDER: S-EPMC12169670 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature