Functional Characterization of Residues Affecting the Catalytic Activity of Glucosyltransferase from Streptococcus mutans

• DOI: 10.1021/acs.jpcb.4c07136
• Publication Date: 2025-05-19T17:07:19Z
• Authors: Lubna Atta; Mamona Mushtaq; Ali Raza Siddiqui; Mohammad Nur-e-Alam; Aftab Ahmed; Zaheer Ul-Haq
• Keywords: Glucosyltransferases; Characterization

Dental caries is a multifactorial, biofilm-mediated disease primarily caused by Streptococcus mutans, key etiological agent. This bacterium secretes extracellular enzymes known as glucosyltransferases (Gtfs), also termed glucansucrases, which play pivotal role in the synthesis of exopolysaccharides through metabolism dietary sucrose. These provide binding sites for attachment and colonization other microorganisms, contributing to initiation progression dental caries. study investigates catalytic mechanisms from S. mutans using molecular dynamics simulations, with focus on conformational interactions amino acid residues that modulate enzymatic activity. Wild-type mutant models glucosyltransferase, bound maltose, sucrose (substrates), acarbose (an inhibitor), were generated analyze patterns these molecules. The systems' stability was assessed root-mean-square deviation, fluctuation, radius gyration, principal component analysis, free energy landscape, dynamic cross-correlation matrix analysis. MMGBSA method employed evaluate relative energies systems. Our findings revealed mutations increased sucrose-bound system while decreasing acarbose-bound system, consistent fluctuation observed across different ligands. changes glucosyltransferase behavior could influence its efficiency.