Comparative structural analysis of different mycobacteriophage-derived mycolylarabinogalactan esterases (Lysin B)

Ahmed H. Korany, Adel Abouhmad, Walid Bakeer, Tamer Essam, Magdy A. Amin, Rajni Hatti-Kaul, Tarek Dishisha

Research output: Contribution to journalArticlepeer-review


Mycobacteriophage endolysins have emerged as a potential alternative to the current antimycobacterial agents. This study focuses on mycolylarabinogalactan hydrolase (LysB) enzymes of the α/β-hydrolase family, which disrupt the unique mycolic acid layer of mycobacterium cell wall. Multiple sequence alignment and structural analysis studies showed LysB-D29, the only enzyme with a solved three-dimensional structure, to share several common features with esterases (lacking lid domain) and lipases (acting on long chain lipids). Sequence and structural comparisons of 30 LysB homology models showed great variation in domain organizations and total protein length with major differences in the loop-5 motif harboring the catalytic histidine residue. Docking of different p-nitrophenyl ligands (C4-C18) to LysB-3D models revealed that the differences in length and residues of loop-5 contributed towards wide diversity of active site conformations (long tunnels, deep and superficial funnels, shallow bowls, and a narrow buried cave) resembling that of lipases, cutinases, and esterases. A set of seven LysB enzymes were recombinantly produced; their activity against p-nitrophenyl esters could be related to their active site conformation and acyl binding site. LysB-D29 (long tunnel) showed the highest activity with long chain p-nitrophenyl palmitate followed by LysB-Omega (shallow bowl) and LysB-Saal (deep funnel).

Original languageEnglish
Article number45
Issue number1
Publication statusPublished - 2019 Dec 27

Subject classification (UKÄ)

  • Structural Biology


  • LysB homology models
  • Molecular docking
  • Multiple sequence alignment
  • Mycolylarabinogalactan esterases
  • α/β-hydrolase family


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