Comparative analysis of SilA-laccase mediated degradation of ciprofloxacin, norfloxacin and ofloxacin and interpretation of the possible catalytic mechanism

Abstract

Fluoroquinolones (FQs) are the most commonly used antimicrobial drugs and regardless of their advantages in the healthcare sector, the pollution of these antimicrobial drugs in the environment has big concerns about human and environmental health. The presence of these antibiotic drugs even at the lowest concentrations in the environment has resulted in the emergence and spread of antibiotic resistance. Hence, it is necessary to remediate these pollutants from the environment. Previously alkaline laccase (SilA) from Streptomyces ipomoeae has been demonstrated to show degrading potentials against two of the FQs, Ciprofloxacin (CIP) and Norfloxacin (NOR); however, the molecular mechanism was not elucidated in detail. In this study, we have analyzed the possible molecular catalytic mechanism of FQ degrading SilA-laccase for the degradation of the FQs, CIP, NOR and Ofloxacin (OFL) using three-dimensional protein structure modeling, molecular docking and molecular dynamic (MD) studies. The comparative protein sequence analysis revealed the presence of tetrapeptide conserved catalytic motif, His¹⁰²-X-His¹⁰⁴-Gly¹⁰⁵. After evaluating the active site of the enzyme in depth using CDD, COACH and S-site tools, we have identified the catalytic triad composed of three conserved amino acid residues, His¹⁰², Val¹⁰³ and Tyr¹⁰⁸ with which ligands interacted during the catalysis process. By analyzing the MD trajectories, it is revealed that the highest degradation potential of SilA is for CIP followed by NOR and OFL. Ultimately, this study provides the possible comparative catalytic mechanism for the degradation of CIP, NOR and OFL by the SilA enzyme.

Communicated by Ramaswamy H. Sarma

Keywords:

• Fluoroquinolones
• SilA-like protein
• molecular dynamic simulation
• molecular docking
• biodegradation potential

Acknowledgments

Central University of Himachal Pradesh, Dharamshala, and Babasaheb Bhimrao Ambedkar University, Lucknow are thanked for providing the research infrastructure used during this study.

Disclosure statement

Authors declare that they have no competing interests to declare.

Additional information

Funding

SB gratefully acknowledged University Grants Commission, India for the Junior Research Fellowship; however, the funding body had no involvement in conducting of the study.