1c0t
From Proteopedia
(New page: 200px<br /> <applet load="1c0t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c0t, resolution 2.7Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1c0t.gif|left|200px]]<br /> | + | [[Image:1c0t.gif|left|200px]]<br /><applet load="1c0t" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1c0t" size=" | + | |
caption="1c0t, resolution 2.7Å" /> | caption="1c0t, resolution 2.7Å" /> | ||
'''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH BM+21.1326'''<br /> | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH BM+21.1326'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have determined the crystal structures of thiazoloisoindolinone | + | We have determined the crystal structures of thiazoloisoindolinone non-nucleoside inhibitors in complex with HIV-1 reverse transcriptase to high-resolution limits of 2.7 A (BM +21.1326) and 2. 52 A (BM +50.0934). We find that the binding modes of this series of inhibitors closely resemble that of "two-ring" non-nucleoside reverse transcriptase inhibitors. The structures allow rationalization of stereochemical requirements, structure-activity data, and drug resistance data. Comparisons with our previous structures suggest modifications to the inhibitors that might improve resilience to drug-resistant mutant forms of reverse transcriptase. Comparison with earlier modeling studies reveals that the predicted overlap of thiazoloisoindolinones with TIBO was largely correct, while that with nevirapine was significantly different. |
==About this Structure== | ==About this Structure== | ||
| - | 1C0T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with BM1 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http:// | + | 1C0T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=BM1:'>BM1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C0T OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: RNA-directed DNA polymerase]] | [[Category: RNA-directed DNA polymerase]] | ||
| - | [[Category: Esnouf, R | + | [[Category: Esnouf, R M.]] |
| - | [[Category: Hopkins, A | + | [[Category: Hopkins, A L.]] |
[[Category: Ren, J.]] | [[Category: Ren, J.]] | ||
| - | [[Category: Stammers, D | + | [[Category: Stammers, D K.]] |
| - | [[Category: Stuart, D | + | [[Category: Stuart, D I.]] |
[[Category: BM1]] | [[Category: BM1]] | ||
[[Category: aids]] | [[Category: aids]] | ||
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[[Category: non-nucleoside inhibitor]] | [[Category: non-nucleoside inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:01:10 2008'' |
Revision as of 10:01, 21 February 2008
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CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH BM+21.1326
Overview
We have determined the crystal structures of thiazoloisoindolinone non-nucleoside inhibitors in complex with HIV-1 reverse transcriptase to high-resolution limits of 2.7 A (BM +21.1326) and 2. 52 A (BM +50.0934). We find that the binding modes of this series of inhibitors closely resemble that of "two-ring" non-nucleoside reverse transcriptase inhibitors. The structures allow rationalization of stereochemical requirements, structure-activity data, and drug resistance data. Comparisons with our previous structures suggest modifications to the inhibitors that might improve resilience to drug-resistant mutant forms of reverse transcriptase. Comparison with earlier modeling studies reveals that the predicted overlap of thiazoloisoindolinones with TIBO was largely correct, while that with nevirapine was significantly different.
About this Structure
1C0T is a Protein complex structure of sequences from Human immunodeficiency virus 1 with as ligand. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
Reference
Crystallographic analysis of the binding modes of thiazoloisoindolinone non-nucleoside inhibitors to HIV-1 reverse transcriptase and comparison with modeling studies., Ren J, Esnouf RM, Hopkins AL, Stuart DI, Stammers DK, J Med Chem. 1999 Sep 23;42(19):3845-51. PMID:10508433
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