In Silico Quest for Putative Drug Targets in Helicobacter Pylori HPAG1: Molecular Modeling of Candidate Enzymes from Lipopolysaccharide Biosynthesis Pathway
EPrints@IICB
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Title |
In Silico Quest for Putative Drug Targets in Helicobacter Pylori HPAG1: Molecular Modeling of Candidate Enzymes from Lipopolysaccharide Biosynthesis Pathway |
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Creator |
Sarkar, Munmun
Maganti, Lakshmi Ghoshal, Nanda Dutta, Chitra |
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Subject |
Structural Biology & Bioinformatics
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Description |
Aimed at identification and structural characterization of novel putative therapeutic targets in H. pylori, the etiological agent of numerous gastrointestinal diseases including peptic ulcer and gastric cancer, the present study comprised of three phases. First, through subtractive analysis of metabolic pathways of Helicobacter pylori HPAG1 and human, as documented in the KEGG database, 11 pathogen-specific pathways were identified. Next, all proteins involved in these pathogen-specific pathways were scrutinized in search of promising targets and the study yielded 25 candidate target proteins that are likely to be essential for the pathogen viability, but have no homolog in human. The lipopolysaccharide (LPS) biosynthesis pathway was found to be the largest contributor (nine proteins) to this list of candidate proteins. Considering the importance of LPS in H. pylori virulence, 3D structural models of three predicted target enzymes of this pathway, namely 2- dehydro-3-deoxy-phosphooctonate aldolase, UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosamine deacetylase and Phosphoheptose isomerase, were then built up using the homology modeling approaches. Binding site analysis and docking of the known biological substrate PEP to 2-dehydro- 3-deoxyphosphooctonate aldolase revealed the potential binding pocket present in the single monomeric form of the enzyme and identified 11 amino acid residues that might play the key roles in this protein-ligand interaction |
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Publisher |
Springer Verlag
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Date |
2012
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/1485/1/APPLIED_BIOCHEMISTRY_AND_BIOTECHNOLOGY___166(_8_)1991%2D2006;2012[26].pdf
Sarkar, Munmun and Maganti, Lakshmi and Ghoshal, Nanda and Dutta, Chitra (2012) In Silico Quest for Putative Drug Targets in Helicobacter Pylori HPAG1: Molecular Modeling of Candidate Enzymes from Lipopolysaccharide Biosynthesis Pathway. Journal of Molecular Modeling, 18 (5). pp. 1855-1866. |
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Relation |
http://dx.doi.org/10.1007/s00894-011-1204-3
http://www.eprints.iicb.res.in/1485/ |
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