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Homology modeling, substrate docking, and molecular simulation studies of mycobacteriophage Che12 lysin A

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Abstract

Mycobacteriophages produce lysins that break down the host cell wall at the end of lytic cycle to release their progenies. The ability to lyse mycobacterial cells makes the lysins significant. Mycobacteriophage Che12 is the first reported temperate phage capable of infecting and lysogenising Mycobacterium tuberculosis. Gp11 of Che12 was found to have Chitinase domain that serves as endolysin (lysin A) for Che12. Structure of gp11 was modeled and evaluated using Ramachandran plot in which 98 % of the residues are in the favored and allowed regions. Che12 lysin A was predicted to act on NAG-NAM-NAG molecules in the peptidoglycan of cell wall. The tautomers of NAG-NAM-NAG molecule were generated and docked with lysin A. The stability and binding affinity of lysin A – NAG-NAM-NAG tautomers were studied using molecular dynamics simulations.

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Acknowledgments

Ms. Shainaba A Saadhali is a recipient of Senior Research fellowship from Lady Tata Memorial Trust, Mumbai, India. The authors would like to thank Dr. P. Velmurugan, Head of the Department, Department of Biophysics, University of Madras, Chennai, India, for his valuable suggestions. The support and fund provided by National Institute for Research in Tuberculosis (NIRT), Chennai, India, is highly acknowledged. The authors would like to thank Mr. R. Senthil Nathan, NIRT Library, for correcting the figures.

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Authors and Affiliations

  1. Department of Bacteriology, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600031, India

    Shainaba A Saadhali, Uma Devi Ranganathan & Vanaja Kumar

  2. Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chennai, 600031, India

    Sameer Hassan

  3. Department of Clinical Research, National Institute for Research in Tuberculosis, Chennai, 600031, India

    Luke Elizabeth Hanna

Authors
  1. Shainaba A Saadhali
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  2. Sameer Hassan
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  3. Luke Elizabeth Hanna
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  4. Uma Devi Ranganathan
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  5. Vanaja Kumar
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Corresponding author

Correspondence to Vanaja Kumar.

Electronic supplementary material

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Supplementary Fig. 1

Ramachandran plot. The Ramachandran plot shows that 98 % of the residues are in the most favored and allowed regions of the plot for the modeled gp11 of Che12 (DOC 111 kb)

Supplementary Fig. 2

Conformations of the 31 tautomers. The docked pose of the 31 NAG-NAM-NAG tautomers within the binding site of Che12 gp11 protein. The NAG-NAM-NAG molecule is represented in green color and the binding sites in wire frame and ribbon form (DOC 540 kb)

Supplementary Table 1

GOLD score for the 31 tautomers generated for NAG-NAM-NAG molecule (DOC 45 kb)

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Saadhali, S.A., Hassan, S., Hanna, L.E. et al. Homology modeling, substrate docking, and molecular simulation studies of mycobacteriophage Che12 lysin A. J Mol Model 22, 180 (2016). https://doi.org/10.1007/s00894-016-3056-3

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  • DOI: https://doi.org/10.1007/s00894-016-3056-3

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