title: Homology modeling of hemagglutinin/protease [HA/P (vibriolysin)] from Vibrio cholerae: sequence comparision, residue interactions and molecular mechanism.
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 alpha + beta 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 S1' 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.
authors: Center of Biotechnology, University of Peshawar, Peshawar, Pakistan.
authors: Ghosia
authors: G
authors: Lutfullah
authors: Farhat
authors: F
authors: Amin
authors: Zahid
authors: Z
authors: Khan
authors: Noreen
authors: N
authors: Azhar
authors: M Kamran
authors: MK
authors: Azim
authors: Sajid
authors: S
authors: Noor
authors: Khalida
authors: K
authors: Shoukat
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D004151:Dipeptides / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry; D008024:Ligands; D008666:Metalloendopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D014734:Vibrio cholerae
chemical_list: D001426:Bacterial Proteins; D004151:Dipeptides; D004791:Enzyme Inhibitors; D008024:Ligands; C529879:N-(1-carboxy-3-phenylpropyl)phenylalanyl-asparagine; D008666:Metalloendopeptidases; C039814:hemagglutinin-protease; C043859:pseudolysin, Pseudomonas aeruginosa