2aid
From Proteopedia
(New page: 200px<br /> <applet load="2aid" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aid, resolution 1.9Å" /> '''STRUCTURE OF A NON-P...) |
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| - | [[Image:2aid.gif|left|200px]]<br /> | + | [[Image:2aid.gif|left|200px]]<br /><applet load="2aid" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2aid" size=" | + | |
caption="2aid, resolution 1.9Å" /> | caption="2aid, resolution 1.9Å" /> | ||
'''STRUCTURE OF A NON-PEPTIDE INHIBITOR COMPLEXED WITH HIV-1 PROTEASE: DEVELOPING A CYCLE OF STRUCTURE-BASED DRUG DESIGN'''<br /> | '''STRUCTURE OF A NON-PEPTIDE INHIBITOR COMPLEXED WITH HIV-1 PROTEASE: DEVELOPING A CYCLE OF STRUCTURE-BASED DRUG DESIGN'''<br /> | ||
==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== | ||
| - | 2AID is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus] with CL and THK as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http:// | + | 2AID is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=THK:'>THK</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AID OCA]. |
==Reference== | ==Reference== | ||
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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]] | ||
| Line 26: | Line 25: | ||
[[Category: non-peptide inhibitor]] | [[Category: non-peptide inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:27:42 2008'' |
Revision as of 14:27, 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
2AID 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
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