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Identifying chemicals with potential therapy of HIV based on protein-protein and protein-chemical interaction network.

Li BQ, Niu B, Chen L, Wei ZJ, Huang T, Jiang M, Lu J, Zheng MY, Kong XY, Cai YD - PLoS ONE (2013)

Bottom Line: In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention.In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy.In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.

ABSTRACT
Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs.

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Three-dimensional structure of HIV-1 PR based on PDB structure 1EBZ drawn with software Pymol.HIV-1 PR is in green. Ligand is in orange, red and blue.
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pone-0065207-g007: Three-dimensional structure of HIV-1 PR based on PDB structure 1EBZ drawn with software Pymol.HIV-1 PR is in green. Ligand is in orange, red and blue.

Mentions: HIV-1 protease is a C2-symmetric homodimer including two monomers which have the identical polypeptide sequence with 99 residues (see Fig. 7) [69]. There is an active site (Asp-Thr-Gly) in the region between P25 and P27. The two subunits are connected by four β anti-parallel strands containing glycine, and each strand contains N-terminal domain and C-terminal domain. Both the monomers have a long “cavity” structure, on the bottom of which lie the catalytic aspartyl residues with planar configuration [69], [70]. Due to the special structure of HIV-1 PR, the substrate peptide binds to the enzyme in an extended anti-parallel β sheet through the amino acid side chains from completely opposite directions [71]. It should be noted that the two subunits of enzyme are not completely identical, although they are symmetrical. Both the monomers have a “flap” structure which is made up of antiparallel β strands extending to subsite P1 and P2’ [72]. Due to the different conformation of ‘flap’ of the two subunits, such a symmetrical conformation has the ability to recognize particular amino acid residues to control the substrates/inhibitors’ access.


Identifying chemicals with potential therapy of HIV based on protein-protein and protein-chemical interaction network.

Li BQ, Niu B, Chen L, Wei ZJ, Huang T, Jiang M, Lu J, Zheng MY, Kong XY, Cai YD - PLoS ONE (2013)

Three-dimensional structure of HIV-1 PR based on PDB structure 1EBZ drawn with software Pymol.HIV-1 PR is in green. Ligand is in orange, red and blue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675210&req=5

pone-0065207-g007: Three-dimensional structure of HIV-1 PR based on PDB structure 1EBZ drawn with software Pymol.HIV-1 PR is in green. Ligand is in orange, red and blue.
Mentions: HIV-1 protease is a C2-symmetric homodimer including two monomers which have the identical polypeptide sequence with 99 residues (see Fig. 7) [69]. There is an active site (Asp-Thr-Gly) in the region between P25 and P27. The two subunits are connected by four β anti-parallel strands containing glycine, and each strand contains N-terminal domain and C-terminal domain. Both the monomers have a long “cavity” structure, on the bottom of which lie the catalytic aspartyl residues with planar configuration [69], [70]. Due to the special structure of HIV-1 PR, the substrate peptide binds to the enzyme in an extended anti-parallel β sheet through the amino acid side chains from completely opposite directions [71]. It should be noted that the two subunits of enzyme are not completely identical, although they are symmetrical. Both the monomers have a “flap” structure which is made up of antiparallel β strands extending to subsite P1 and P2’ [72]. Due to the different conformation of ‘flap’ of the two subunits, such a symmetrical conformation has the ability to recognize particular amino acid residues to control the substrates/inhibitors’ access.

Bottom Line: In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention.In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy.In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.

ABSTRACT
Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs.

Show MeSH
Related in: MedlinePlus