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

Korany, Ahmed H. ; Abouhmad, Adel LU ; Bakeer, Walid ; Essam, Tamer LU ; Amin, Magdy A. ; Hatti-Kaul, Rajni LU and Dishisha, Tarek LU (2019) In Biomolecules 10(1).
Abstract

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... (More)

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).

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
LysB homology models, Molecular docking, Multiple sequence alignment, Mycolylarabinogalactan esterases, α/β-hydrolase family
in
Biomolecules
volume
10
issue
1
article number
45
publisher
Multidisciplinary Digital Publishing Institute (MDPI)
external identifiers
  • pmid:31892223
  • scopus:85077379114
ISSN
2218-273X
DOI
10.3390/biom10010045
language
English
LU publication?
yes
id
95561c72-262c-4cbf-86af-ea9982008658
date added to LUP
2020-01-20 16:39:09
date last changed
2020-11-24 01:36:29
@article{95561c72-262c-4cbf-86af-ea9982008658,
  abstract     = {<p>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).</p>},
  author       = {Korany, Ahmed H. and Abouhmad, Adel and Bakeer, Walid and Essam, Tamer and Amin, Magdy A. and Hatti-Kaul, Rajni and Dishisha, Tarek},
  issn         = {2218-273X},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Multidisciplinary Digital Publishing Institute (MDPI)},
  series       = {Biomolecules},
  title        = {Comparative structural analysis of different mycobacteriophage-derived mycolylarabinogalactan esterases (Lysin B)},
  url          = {http://dx.doi.org/10.3390/biom10010045},
  doi          = {10.3390/biom10010045},
  volume       = {10},
  year         = {2019},
}