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Since the introduction of β-lactam antibiotics, disease causing microbial resistance to these antibiotics has become a problem increasingly. Discovery of functional residues in beta-lactamase that play major role in antibiotic resistance provide an opportunity to understand their fundamental molecular mechanisms. We present an example of extraction of functional information from protein 3D structures using a bioinformatics approach in the context of the antibiotic resistance. In case studies, 45 homologous beta-lactamase sequences were investigated using a homology based approach by ConSurf server to analyse the surface of beta-lactamase to reveal common functional features which might facilitate them to identify lactam antibiotics. We have identified functional residues using phylogenetic studies, protein sequence MSA and three-dimensional mapping. The results demonstrate the presence of antibiotic resistance specific highly conserved residues comprising of high proportion of surface-exposed hydrophobic residues as do not endure amino acid substitutions, signifying that they have critical role in antibiotic resistance and the remaining positions tolerate amino acid substitutions and may affect the substrate specificity of the beta lactamase. These functionally important residues could also potentially be used in the rational design of novel, efficient antimicrobial agents
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Author(s): Rajendra Mandage Padmaja Kamath Monali Wakle Afaque Momin
beta-lactamase, drug resistance, 3D structure, functional residues, ConSurf server, PSI-BLAST.