The Protein Journal

, Volume 27, Issue 2, pp 105–114

Homology Modeling of Hemagglutinin/Protease [HA/P (vibriolysin)] from Vibrio Cholerae: Sequence Comparision, Residue Interactions and Molecular Mechanism

  • Ghosia Lutfullah
  • Farhat Amin
  • Zahid Khan
  • Noreen Azhar
  • M. Kamran Azim
  • Sajid Noor
  • Khalida Shoukat
Article

DOI: 10.1007/s10930-007-9113-0

Cite this article as:
Lutfullah, G., Amin, F., Khan, Z. et al. Protein J (2008) 27: 105. doi:10.1007/s10930-007-9113-0

Abstract

Vibrio cholerae produces a zinc-containing and calcium-stabilized soluble hemagglutinin/protease, which has been earlier shown to have the ability to cleave several physiologically important substrates including mucin, fibronectin and lactoferin. This study presents homology modeling of hemagglutinin/protease (vibriolysin) from Vibrio cholerae in the presence of inhibitor HPI [N-(1-carboxy-3-phenylpropyl)-phenylalanyl-alpha-aspargine]. The 3D structure was predicted based on its sequence homology with Pseudomonas aeruginosa elastase (PAE). Comparison of the 3D structures of PAE and HA/P reveals a remarkable similarity having a conserved α + β domain. The inhibitor shows similar binding features as seen in other metalloproteases of M4 peptidase family. The study also highlights the key catalytic residues as well as the residues at the S1 and \( {\text{S}}_{{\text{1}}} ^{\prime } \) binding sub-sites. The similarities between the two proteins provide support for the hypothesis that the two enzymes have similar three-dimensional structures and a common mechanism of action. The fact that both enzymes are secreted as zinc-containing proteases, led us to further hypothesize that they may play similar role in pathogenesis.

Keywords

Vibrio cholerae Vibriolysin Hemagglutinin Homology modeling Pathogenesis Enzyme substrate interactions 

Abbreviations

CT

Cholera toxin

Ace

Accessory cholera enterotoxin

Zot

Zonula occludens toxin

HA/P

Hemagglutinin/protease

PAE

Pseudomonas aeruginosa elastase

TLPs

Thermolysin-like proteases

HPI

N-(1-Carboxy-3-phenylpropyl)-phenylalanyl-alpha-aspargine

TLN

Thermolysin

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Ghosia Lutfullah
    • 1
  • Farhat Amin
    • 1
  • Zahid Khan
    • 1
  • Noreen Azhar
    • 1
  • M. Kamran Azim
    • 2
  • Sajid Noor
    • 2
  • Khalida Shoukat
    • 2
  1. 1.Center of BiotechnologyUniversity of PeshawarPeshawarPakistan
  2. 2.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan

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