Computational prediction of active sites and ligands in different AHL quorum quenching lactonases and acylases
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Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
Computational prediction of active sites and ligands in different AHL quorum quenching lactonases and acylases ZULKAR NAIN1 , UTPAL KUMAR ADHIKARI2 , FARUQ ABDULLA3, NAHID HOSSAIN1, NIRMAL CHANDRA BARMAN1, FARIHA JASIN MANSUR4, HIROYUKI AZAKAMI4 and MOHAMMAD MINNATUL KARIM1* 1
Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh 2
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
3
Department of Statistics, Faculty of Science, Islamic University, Kushtia 7003, Bangladesh 4
Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan *Corresponding author (Email, [email protected])
MS received 19 December 2018; accepted 30 October 2019 With the emergence of multidrug-resistant ‘superbug’, conventional treatments become obsolete. Quorum quenching (QQ), enzyme-dependent alteration of quorum sensing (QS), is now considered as a promising antimicrobial therapy because of its potentiality to impede virulence gene expression without resulting in growth inhibition and antibiotic resistance. In our study, we intended to compare between two major QQ enzyme groups (i.e., AHL lactonases and AHL acylases) in terms of their structural and functional aspects. The amino acid composition-based principal component analysis (PCA) suggested that probably there is no structural and functional overlapping between the two groups of enzymes as well as within the lactonase enzymes but the acylases may functionally be affected by one another. In subcellular localization analysis, we also found that most lactonases are cytoplasmic while acylases are periplasmic. Investigation on the secondary structural features showed random coil dominates over a-helix and b-sheet in all evaluated enzymes. For structural comparison, the tertiary structures of the selected proteins were modelled and submitted to the PMDB database (Accession ID: PM0081007 to PM0081018). Interestingly, sequence alignment revealed the presence of several conserved domains important for functions in both protein groups. In addition, three amino acid residues, namely aspartic acid, histidine, and isoleucine, were common in the active sites of all protein models while most frequent ligands were found to be 3C7, FEO, and PAC. Importantly, binding interactions of predicted ligands were similar to that of native QS signal molecules. Furthermore, hydrogen bonds analysis suggested six proteins are more stable than others. We believe that the knowledge of this comparative study could be useful for further research in the development of QSbased universal antibacterial strategies. Keywords. Quorum quenching; quorum sensing; acyl homoserine lactones; AHL lactonase; AHL acylases; principal component analysis Abbreviations: QQ, quorum quenching; QS, quorum sensing; QQE, quorum quenching enzyme; AHL, acyl-homoserine lactone; HSL, homoserine lactone; MSA, multiple sequ
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