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Structural analysis and molecular docking of potential ligands with chorismate synthase of <i style="mso-bidi-font-style: normal">Listeria monocytogenes</i>: A novel antibacterial drug target

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Title Structural analysis and molecular docking of potential ligands with chorismate synthase of Listeria monocytogenes: A novel antibacterial drug target
 
Creator Hossain, Md. Musharaf
Roy, Pradip Kumar
Mosnaz, A T M Jannatul
Shakil, Shahriar Kabir
Hasan, Md. Mehedi
Prodhan, Shamsul H
 
Subject Virtual screening
Listeria monocytogenes
Chorismate synthase
Molecular docking
 
Description 45-59
Listeriosis, in particular that caused by Listeria monocytogenes, is
a major foodborne pathogen, and its control is becoming
difficult because of widespread emergence of drug resistance strains.
Chorismate synthase (CS), an essential enzyme of shikimate pathway present only
in bacteria, fungi, plant and some apicomplexan parasites, is a validated
potential antimicrobial drug target. Antimicrobial development through the
elucidation of essential structural features of the CS of
L. monocytogenes (LmCS), identification and prioritization
of potential lead compounds targeted against LmCS were done.
Structure-based virtual screening and docking studies were performed using
Autodock tools to retrieve potential candidates with high affinity binding
against LmCS model from several
ligand repositories. The potency of binding was also checked with other
structurally similar CS from Streptococcus pneumoniae (SpCS) and Mycobacterium tuberculosis (MtCS).
The sequence and structural studies revealed LmCS was similar to be other
CS structures (1Q1L, 1QXO, 1R52, 1R53, 1SQ1, 1UM0, 1UMF, 1ZTB, 2011, 2012, 4ECD and 2G85) with each monomer presenting β-α-β
sandwich topology with a central helical core. Molecular docking studies and
ADME/Tox results revealed that ZINC03803450 and ZINC20149031 were most potent molecules binding
into the active site of LmCS. Other two ligands ZINC13387711 and
ZINC16052528 showed a strong binding affinity score against all three
structures (LmCS, SpCS and MtCS) and bind to LmCS
with the predicted inhibition constant (Ki) values of 22.94 nM and 35.84 nM, respectively. A reported
benzofuran-3[2H]-one analog CHEMBL135212 with good ADME/Tox properties and
experimental IC50 (nM) value of 7000 nM with SpCS
could also be considered as a potential inhibitor of LmCS, as compared
to previously reported 41 benzofuran-3[2H]-one analogs against SpCS. This information will assist in
discovering those compounds that may act as potent CS inhibitors. Further
experimental studies and evaluation of structure-activity relationship could help in the development
of potential inhibitors against listeriosis, as well as antibacterial
chemotherapy.
 
Date 2015-03-30T05:00:30Z
2015-03-30T05:00:30Z
2015-03-30T05:00:30Z
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/31262
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Source IJBB Vol.52(1) [February 2015]