Comparative modeling and in silico characterization of FtsH from Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) is a major global health problem causing over one million deaths per year. The causative agent
responsible for causing TB is Mycobacterium tuberculosis. In host-parasite diseases like tuberculosis, proteins as drug target are
first preference. Multidrug-Resistant Tuberculosis (MDR TB) occurs when Mycobacterium tuberculosis strain is resistant to
isoniazid and rifampin, two of the most powerful first-line drugs. FtsH is a membrane bound ATP dependent Zinc-metalloprotease
which proteolytically regulates the level of specific membrane and cytoplasmic proteins that participate in diverse cellular
function. FtsH is essential membrane – bound protease that degrades integral membrane proteins as well as cytoplasmic proteins.
Aim: The objectives of the present study are to determine the three- dimensional (3D) structure of topological domain of FtsH
from Mycobacterium tuberculosis using comparative modeling and its in silico characterization. Methodology: The sequence for
FtsH was retrieved from UNIPROT database and sequence analysis was carried out using BLAST and FUGUE for the selection of
template. The crystal structure of FtsH from Thermatogamaritima was selected as a template. The protein modeling was carried
out using ModWeb and Swissmodeller. The obtained 3D model of the FtsH was visualized and analyzed using Chimera. This
modeled protein structure was refined by loop modeling. Later, the quality of the protein structure was verified by its energy and
stereochemical properties. Further, the in sillico characterization of the FtsH was carried out. Result: The 3D structure of FtsH,
obtained from this study can be used in developing novel inhibitors using the methods of rational drug designing