In-Silico Structural and Functional Characterization of a V. cholerae O395 Hypothetical Protein Containing a PDZ1 and an Uncommon Protease Domain
Chaudhuri K (2013) In-Silico Structural and Functional Characterization of a V. cholerae O395 Hypothetical Protein Containing a
PDZ1 and an Uncommon Protease Domain. PLoS ONE 8(2): e56725. doi:10.1371/journal.pone.0056725
In-Silico Structural and Functional Characterization of a V. cholerae O395 Hypothetical Protein Containing a PDZ1 and an Uncommon Protease Domain
Avirup Dutta 0
Atul Katarkar 0
Keya Chaudhuri 0
Eugene A. Permyakov, Russian Academy of Sciences, Institute for Biological Instrumentation, Russian Federation
0 1 CSIR-SRF, Molecular and Human Genetics Division, CSIR - Indian Institute of Chemical Biology , Kolkata, West Bengal , India , 2 ICMR-SRF , Molecular and Human Genetics Division, CSIR - Indian Institute of Chemical Biology , Kolkata, West Bengal , India , 3 Chief Scientist , Molecular and Human Genetics Division, and Head Academic Affairs Division, CSIR - Indian Institute of Chemical Biology , Kolkata, West Bengal , India
Vibrio cholerae, the causative agent of epidemic cholera, has been a constant source of concern for decades. It has constantly evolved itself in order to survive the changing environment. Acquisition of new genetic elements through genomic islands has played a major role in its evolutionary process. In this present study a hypothetical protein was identified which was present in one of the predicted genomic island regions of the large chromosome of V. cholerae O395 showing a strong homology with a conserved phage encoded protein. In-silico physicochemical analysis revealed that the hypothetical protein was a periplasmic protein. Homology modeling study indicated that the hypothetical protein was an unconventional and atypical serine protease belonging to HtrA protein family. The predicted 3D-model of the hypothetical protein revealed a catalytic centre serine utilizing a single catalytic residue for proteolysis. The predicted catalytic triad may help to deduce the active site for the recruitment of the substrate for proteolysis. The active site arrangements of this predicted serine protease homologue with atypical catalytic triad is expected to allow these proteases to work in different environments of the host.
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. These authors contributed equally to this work.
Vibrio cholerae, the most notable member of the Vibrionaceae family
is the etiological agent of epidemic cholera, causing a severe and
sometimes lethal diarrheal disease. V. cholerae is classified into two
serogroups: O1 and nonO1. So far, the toxigenic strains of
serogroups O1 and O139 have been found to cause cholera
epidemics. There are two biotypes of V. cholerae O1, Classical and
El Tor. There have been seven major pandemics since 1817.
Isolates of the sixth pandemic were of O1 classical biotype [1].
The complete genome of V. cholerae classical biotype has been
sequenced, which revealed that the genome is composed of two
chromosomes, the large and the small chromosome [2].
Cumulatively 3875 genes have been identified. However, 1402 open
reading frames, code for hypothetical proteins, the functions of
which are not known.
V. cholerae infection is noninvasive. In this organism, the two
major virulence factors cholera toxin (CT) and toxin corregulated
pili (TCP) have been reported to be encoded on mobile genetic
elements. Gene acquisition and other genomic alterations, by the
mechanism of Horizontal gene transfer have always played a
critical role in the adaptive evolution of prokaryotes. Genomic
Islands (GIs) in prokaryotic genomes often contain horizontally
transferred genetic materials as evident from the presence of
integrase, transposons, phage mediated genes, etc. in these islands
[35]. These genomic islands are therefore of critical importance
in the evolution of the prokaryotic genomes, their pathogenicity
and other special function.
The ctxAB genes coding for CT are encoded on a filamentous
bacteriophage CTXQ [6]. TCP, an essential colonization factor,
was originally designated as part of a pathogenicity island named
Vibrio pathogenicity island VPI, but this island has later on been
proposed to be the genome of a filamentous phage, VPIQ [7].
Clinical trials on volunteers using vaccine strains of V. cholerae in
which several toxin genes including the cholera toxin were
eliminated were performed. Results of those trails showed mild to
moderate diarrhea in the subjects clearly suggesting that there are
yet to be determined virulence factors in the V. cholerae genome [8].
In order to survive distinct stress situations and prevent the
accumulation of misfolded and aggregated proteins, all cells
employ an efficient protein quality control system consisting of
molecular chaperones [9,10] in order to prevent cellular
malfunctions and even cell death [11,12]. The high temperature
requirement A (HtrA) family of proteases are involved in the key
aspects of protein quality control [13]. In Escherichia coli they have
been reported to monitor the proper folding and the functioning of
the proteins in ce (...truncated)