1idb
From Proteopedia
(New page: 200px<br /> <applet load="1idb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1idb, resolution 2.2Å" /> '''CRYSTAL STRUCTURES O...) |
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| - | [[Image:1idb.gif|left|200px]]<br /> | + | [[Image:1idb.gif|left|200px]]<br /><applet load="1idb" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1idb, resolution 2.2Å" /> | caption="1idb, resolution 2.2Å" /> | ||
'''CRYSTAL STRUCTURES OF HIV-2 PROTEASE IN COMPLEX WITH INHIBITORS CONTAINING THE HYDROXYETHYLAMINE DIPEPTIDE ISOSTERE'''<br /> | '''CRYSTAL STRUCTURES OF HIV-2 PROTEASE IN COMPLEX WITH INHIBITORS CONTAINING THE HYDROXYETHYLAMINE DIPEPTIDE ISOSTERE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The HIV protease is essential for the life cycle of the virus | + | BACKGROUND: The HIV protease is essential for the life cycle of the virus and is an important target for the development of therapeutic treatments against AIDS. The structures of HIV protease in complex with different inhibitors have helped in understanding the interactions between inhibitors and the protease and in the design and optimization of HIV protease inhibitors. RESULTS: We report here crystal structures at up to 1.7 A resolution of the homodimeric HIV-2 protease in complex with seven inhibitors containing the hydroxyethylamine dipeptide isostere. A novel dimethylphenoxyacetyl group that is present in some of these inhibitors is inserted between residues 48' and 49' in the flap of the protease and residues 29' and 30' (where a prime indicates a residue in the second monomer), which undergo a conformational change to accommodate the phenyl ring of the inhibitor. CONCLUSIONS: This study shows that besides the residues in the flap and residues 79-81 in the S1 substrate-binding pocket which undergo conformational changes upon inhibitor binding, residues 29 and 30 can also adapt their conformation to fit certain inhibitors. Conformational flexibility of the HIV protease plays an important role in inhibitor binding. |
==About this Structure== | ==About this Structure== | ||
| - | 1IDB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with DBA and SPY as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1IDB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=DBA:'>DBA</scene> and <scene name='pdbligand=SPY:'>SPY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IDB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Anderson, P | + | [[Category: Anderson, P C.]] |
[[Category: Tong, L.]] | [[Category: Tong, L.]] | ||
[[Category: DBA]] | [[Category: DBA]] | ||
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[[Category: hydrolase(acid proteinase)]] | [[Category: hydrolase(acid proteinase)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:10:37 2008'' |
Revision as of 11:10, 21 February 2008
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CRYSTAL STRUCTURES OF HIV-2 PROTEASE IN COMPLEX WITH INHIBITORS CONTAINING THE HYDROXYETHYLAMINE DIPEPTIDE ISOSTERE
Overview
BACKGROUND: The HIV protease is essential for the life cycle of the virus and is an important target for the development of therapeutic treatments against AIDS. The structures of HIV protease in complex with different inhibitors have helped in understanding the interactions between inhibitors and the protease and in the design and optimization of HIV protease inhibitors. RESULTS: We report here crystal structures at up to 1.7 A resolution of the homodimeric HIV-2 protease in complex with seven inhibitors containing the hydroxyethylamine dipeptide isostere. A novel dimethylphenoxyacetyl group that is present in some of these inhibitors is inserted between residues 48' and 49' in the flap of the protease and residues 29' and 30' (where a prime indicates a residue in the second monomer), which undergo a conformational change to accommodate the phenyl ring of the inhibitor. CONCLUSIONS: This study shows that besides the residues in the flap and residues 79-81 in the S1 substrate-binding pocket which undergo conformational changes upon inhibitor binding, residues 29 and 30 can also adapt their conformation to fit certain inhibitors. Conformational flexibility of the HIV protease plays an important role in inhibitor binding.
About this Structure
1IDB is a Single protein structure of sequence from Human immunodeficiency virus 1 with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structures of HIV-2 protease in complex with inhibitors containing the hydroxyethylamine dipeptide isostere., Tong L, Pav S, Mui S, Lamarre D, Yoakim C, Beaulieu P, Anderson PC, Structure. 1995 Jan 15;3(1):33-40. PMID:7743130
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