1g2k
From Proteopedia
(New page: 200px<br /> <applet load="1g2k" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g2k, resolution 1.95Å" /> '''HIV-1 PROTEASE WITH...) |
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| - | [[Image:1g2k. | + | [[Image:1g2k.jpg|left|200px]]<br /><applet load="1g2k" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1g2k, resolution 1.95Å" /> | caption="1g2k, resolution 1.95Å" /> | ||
'''HIV-1 PROTEASE WITH CYCLIC SULFAMIDE INHIBITOR, AHA047'''<br /> | '''HIV-1 PROTEASE WITH CYCLIC SULFAMIDE INHIBITOR, AHA047'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1G2K 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 NM1 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1G2K 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=NM1:'>NM1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1G2K OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protease inhibitors]] | [[Category: protease inhibitors]] | ||
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Revision as of 13:50, 15 February 2008
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HIV-1 PROTEASE WITH CYCLIC SULFAMIDE INHIBITOR, AHA047
Overview
We have previously reported on the unexpected flipped conformation in the, cyclic sulfamide class of inhibitors. An attempt to induce a symmetric, binding conformation by introducing P2/P2' substituents foreseen to bind, preferentially in the S2/S2' subsite was unsuccessful. On the basis of the, flipped conformation we anticipated that nonsymmetric sulfamide, inhibitors, with P2/P2' side chains modified individually for the S1' and, S2 subsites, should be more potent than the corresponding symmetric, analogues. To test this hypothesis, a set of 18 cyclic sulfamide, inhibitors (11 nonsymmetric and 7 symmetric) with different P2/P2', substituents was prepared and evaluated in an enzyme assay. To rationalize, the structure-activity relationship (SAR) and enable the alignment of the, nonsymmetric inhibitors, i.e., which of the P2/P2' substituents of the, nonsymmetric inhibitors interact with which subsite, a CoMFA study was, performed. The CoMFA model, constructed from the 18 inhibitors in this, study along with seven inhibitors from previous work by our group, has, successfully been used to rationalize the SAR of the cyclic sulfamide, inhibitors. Furthermore, from the information presented herein, the SAR of, the cyclic sulfamide class of inhibitors seems to differ from the SAR of, the related cyclic urea inhibitors reported by DuPont and DuPont-Merck.
About this Structure
1G2K is a Single protein structure of sequence from Human immunodeficiency virus 1 with as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors., Schaal W, Karlsson A, Ahlsen G, Lindberg J, Andersson HO, Danielson UH, Classon B, Unge T, Samuelsson B, Hulten J, Hallberg A, Karlen A, J Med Chem. 2001 Jan 18;44(2):155-69. PMID:11170625
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