1aid
From Proteopedia
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==Overview== | ==Overview== | ||
| - | A stable, non-peptide inhibitor of the protease from type 1 human | + | A stable, non-peptide inhibitor of the protease from type 1 human immunodeficiency virus has been developed, and the stereochemistry of binding defined through crystallographic three-dimensional structure determination. The initial compound, haloperidol, was discovered through computational screening of the Cambridge Structural Database using a shape complementarity algorithm. The subsequent modification is a non-peptidic lateral lead, which belongs to a family of compounds with well characterized pharmacological properties. This thioketal derivative of haloperidol and a halide counterion are bound within the enzyme active site in a mode distinct from the observed for peptide-based inhibitors. A variant of the protease cocrystallized with this inhibitor shows binding in the manner predicted during the initial computer-based search. The structures provide the context for subsequent synthetic modifications of the inhibitor. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Human immunodeficiency virus]] | [[Category: Human immunodeficiency virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fauman, E | + | [[Category: Fauman, E B.]] |
| - | [[Category: Keenan, R | + | [[Category: Keenan, R J.]] |
| - | [[Category: Rutenber, E | + | [[Category: Rutenber, E E.]] |
| - | [[Category: Stroud, R | + | [[Category: Stroud, R M.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: THK]] | [[Category: THK]] | ||
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[[Category: protease]] | [[Category: protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:44:54 2008'' |
Revision as of 09:44, 21 February 2008
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STRUCTURE OF A NON-PEPTIDE INHIBITOR COMPLEXED WITH HIV-1 PROTEASE: DEVELOPING A CYCLE OF STRUCTURE-BASED DRUG DESIGN
Overview
A stable, non-peptide inhibitor of the protease from type 1 human immunodeficiency virus has been developed, and the stereochemistry of binding defined through crystallographic three-dimensional structure determination. The initial compound, haloperidol, was discovered through computational screening of the Cambridge Structural Database using a shape complementarity algorithm. The subsequent modification is a non-peptidic lateral lead, which belongs to a family of compounds with well characterized pharmacological properties. This thioketal derivative of haloperidol and a halide counterion are bound within the enzyme active site in a mode distinct from the observed for peptide-based inhibitors. A variant of the protease cocrystallized with this inhibitor shows binding in the manner predicted during the initial computer-based search. The structures provide the context for subsequent synthetic modifications of the inhibitor.
About this Structure
1AID is a Single protein structure of sequence from Human immunodeficiency virus with and as ligands. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
Structure of a non-peptide inhibitor complexed with HIV-1 protease. Developing a cycle of structure-based drug design., Rutenber E, Fauman EB, Keenan RJ, Fong S, Furth PS, Ortiz de Montellano PR, Meng E, Kuntz ID, DeCamp DL, Salto R, et al., J Biol Chem. 1993 Jul 25;268(21):15343-6. PMID:8340363
Page seeded by OCA on Thu Feb 21 11:44:54 2008
