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PDBsum entry 1hii
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Hydrolase (aspartic proteinase)
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PDB id
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1hii
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Comparative analysis of the X-Ray structures of HIV-1 and HIV-2 proteases in complex with cgp 53820, A novel pseudosymmetric inhibitor.
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Authors
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J.P.Priestle,
A.Fässler,
J.Rösel,
M.Tintelnot-Blomley,
P.Strop,
M.G.Grütter.
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Ref.
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Structure, 1995,
3,
381-389.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The human immunodeficiency virus (HIV) is the causative agent of
acquired immunodeficiency syndrome (AIDS). Two subtypes of the virus, HIV-1 and
HIV-2, have been characterized. The protease enzymes from these two subtypes,
which are aspartic acid proteases and have been found to be essential for
maturation of the infectious particle, share about 50% sequence identity.
Differences in substrate and inhibitor binding between these enzymes have been
previously reported. RESULTS: We report the X-ray crystal structures of both
HIV-1 and HIV-2 proteases each in complex with the pseudosymmetric inhibitor,
CGP 53820, to 2.2 A and 2.3 A, respectively. In both structures, the entire
enzyme and inhibitor could be located. The structures confirmed earlier modeling
studies. Differences between the CGP 53820 inhibitory binding constants for the
two enzymes could be correlated with structural differences. CONCLUSIONS: Minor
sequence changes in subsites at the active site can explain some of the observed
differences in substrate and inhibitor binding between the two enzymes. The
information gained from this investigation may help in the design of equipotent
HIV-1/HIV-2 protease inhibitors.
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Figure 2.
Figure 2. The pseudosymmetrical HIV protease inhibitor CGP
53820. Cha refers to the cyclohexyl ‘side chain’ which binds
in the P1′ pocket of HIV protease. Figure 2. The
pseudosymmetrical HIV protease inhibitor CGP 53820. Cha refers
to the cyclohexyl ‘side chain’ which binds in the P1′
pocket of HIV protease.
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Figure 6.
Figure 6. Stereo illustration of the binding of CGP 53820
(green) to HIV-1 protease (red) superimposed with HIV-2 protease
(blue) in complex with CGP 53820 (yellow). Figure 6. Stereo
illustration of the binding of CGP 53820 (green) to HIV-1
protease (red) superimposed with HIV-2 protease (blue) in
complex with CGP 53820 (yellow).
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1995,
3,
381-389)
copyright 1995.
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Secondary reference #1
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Title
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Novel pseudosymmetric inhibitors of HIV-1 protease
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Authors
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A.Fassler,
J.Rosel,
M.Tintelnot-Blomley,
E.Alteri,
G.Bold,
M.Lang.
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Ref.
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bioorg med chem lett, 1993,
3,
2837.
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