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J Chem Inf Model. 2013 Aug 27. [Epub ahead of print]
Structurally Conserved Binding Sites of Hemagglutinin as Targets for Influenza Drug and Vaccine Development.
Yusuf M, Konc J, Sy Bing C, Trykowska Konc J, Ahmad Khairudin NB, Janezic D, Wahab H.
Abstract
ProBiS is a new method to identify the binding site of protein through local structural alignment against the non-redundant Protein Data Bank (PDB), which may result in unique findings compared to the energy-based, geometry-based, and sequence-based predictors. In this work, binding sites of Hemagglutinin (HA), which is important target for drug/vaccine in influenza treatment, have been revisited by ProBiS. For the first time, the identification of conserved binding sites by local structural alignment across all subtypes and strains of HA available in PDB is presented. ProBiS finds three distinctive conserved sites on HA's structure (named Site 1, Site 2, and Site 3). Compared to other predictors, ProBiS is the only one that accurately defines the receptor binding site (Site 1). Apart from that, Site 2 which is located slightly above the TBHQ binding site is proposed as a potential novel conserved target for membrane fusion inhibitor. Lastly, Site 3, located around Helix-A at the stem domain and recently targeted by cross-reactive antibody is predicted to be conserved in the latest H7N9 China 2013 strain as well. The further exploration of these three sites provides valuable insight in optimizing the influenza drugs and vaccines development.
PMID:
23980878
[PubMed - as supplied by publisher]
Structurally Conserved Binding Sites of Hemagglutinin as Targets for Influenza Drug and Vaccine Development.
Yusuf M, Konc J, Sy Bing C, Trykowska Konc J, Ahmad Khairudin NB, Janezic D, Wahab H.
Abstract
ProBiS is a new method to identify the binding site of protein through local structural alignment against the non-redundant Protein Data Bank (PDB), which may result in unique findings compared to the energy-based, geometry-based, and sequence-based predictors. In this work, binding sites of Hemagglutinin (HA), which is important target for drug/vaccine in influenza treatment, have been revisited by ProBiS. For the first time, the identification of conserved binding sites by local structural alignment across all subtypes and strains of HA available in PDB is presented. ProBiS finds three distinctive conserved sites on HA's structure (named Site 1, Site 2, and Site 3). Compared to other predictors, ProBiS is the only one that accurately defines the receptor binding site (Site 1). Apart from that, Site 2 which is located slightly above the TBHQ binding site is proposed as a potential novel conserved target for membrane fusion inhibitor. Lastly, Site 3, located around Helix-A at the stem domain and recently targeted by cross-reactive antibody is predicted to be conserved in the latest H7N9 China 2013 strain as well. The further exploration of these three sites provides valuable insight in optimizing the influenza drugs and vaccines development.
PMID:
23980878
[PubMed - as supplied by publisher]
