Prediction of Protein Structure of β-LactamaseEnzymes in Mycobacterium Tuberculosis and Drug Prediction Based on AlphaFold3

This study focuses on Rv2068c blaC β-lactamase, a core drug-resistant protein in Mycobacterium tuberculosis (MTB), which compromises the efficacy of β-lactam antibiotics. After investigation of comprehensive analysis of resistance mechanism of Rv2068c blac β-lactamase using the UniProt database, its three-dimentional structure was predicted using AlphaFold 3. The structural model revealed conserved catalytic motifs, including a serine-active site critical for β-lactam ring hydrolysis. Later on, Rv2068c blaC β-lactamase was compared with other TB drug resistance-related β-lactamase proteins (e.g., GES-5, A0A1X1YXR3), which provided data on the nature and classification of β-lactamases which correlate with substrate specificity and enzymatic stability and along with their structural and functional differences. Additionally, docking studies provide ligand-receptor binding modes and affinities. Docking studies identified ligand-receptor binding modes, with DELAMANID and JSF-3285 exhibiting consistent high-affinity interactions across clusters. These findings underscore BlaC’s role in multidrug resistance and provide a structural framework for designing inhibitors against β-lactamase-mediated antibiotic inactivation.