In silico characterization of Leptospira interrogans DNA ligase A and delineation of its antimicrobial stretches

Abstract

In the present study, an attempt is being made to characterize the DNA ligase A (LigA) of Leptospira interrogans by computational methods. Several prediction servers (SwissProt, MoByle, TMHMM, PSIPRED, SignalP, etc.) were used to predict and interpret the physico-chemical parameters associated with LigA. A three-dimensional (3D) structure of the protein was created by homology-based modeling (I-TASSER). DNA-binding regions (PATCHDOCK) and interactome (STRINGS) of the protein were also predicted. A phylogenetic tree was constructed by MEGA version X. Finally, amino acid residues with antimicrobial activity were determined from the LigA sequence by AntiBP server. Domains responsible for oligonucleotide binding (OB), BRCT (BRCA1 carboxy-terminal), and motifs like helix hairpin helix (HhH) were found to be present in the protein designating the super family it belongs to. Moreover, consensus residues, i.e., -KX/IDG- responsible for adenylation, are also found to be conserved within the amino acid sequence. In silico mutational analysis suggested that replacing any of the charged residues in the consensus (K or D) can lead to catalytic instability of the enzyme. Further, the protein was scanned for antimicrobial peptide (AMPs). Ten different stretches were found to have a potential bactericidal effect with significant scores. LigA of Leptospira interrogans is an acidic protein rich in alpha helixes which also contain 10 potential antimicrobial peptides in its amino acid sequence.