1lvj
From Proteopedia
(New page: 200px<br /> <applet load="1lvj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lvj" /> '''STRUCTURE OF TAR RNA COMPLEXED WITH A TAT-T...) |
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| - | [[Image:1lvj.gif|left|200px]]<br /> | + | [[Image:1lvj.gif|left|200px]]<br /><applet load="1lvj" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1lvj" size=" | + | |
caption="1lvj" /> | caption="1lvj" /> | ||
'''STRUCTURE OF TAR RNA COMPLEXED WITH A TAT-TAR INTERACTION NANOMOLAR INHIBITOR THAT WAS IDENTIFIED BY COMPUTATIONAL SCREENING'''<br /> | '''STRUCTURE OF TAR RNA COMPLEXED WITH A TAT-TAR INTERACTION NANOMOLAR INHIBITOR THAT WAS IDENTIFIED BY COMPUTATIONAL SCREENING'''<br /> | ||
==Overview== | ==Overview== | ||
| - | HIV-1 TAR RNA functions critically in viral replication by binding the | + | HIV-1 TAR RNA functions critically in viral replication by binding the transactivating regulatory protein Tat. We recently identified several compounds that experimentally inhibit the Tat-TAR interaction completely at a 100 nM concentration. We used computational screening of the 181,000-compound Available Chemicals Directory against the three-dimensional structure of TAR [1]. Here we report the NMR-derived structure of TAR complexed with acetylpromazine. This structure represents a new class of compounds with good bioavailability and low toxicity that bind with high affinity to TAR. NMR data unambiguously show that acetylpromazine binds only to the unique 5' bulge site to which the Tat protein binds. Specificity and affinity of binding are conferred primarily by a network of base stacking and hydrophobic interactions. Acetylpromazine alters the structure of free TAR less than Tat peptides and neomycin do. |
==About this Structure== | ==About this Structure== | ||
| - | 1LVJ 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 PMZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1LVJ 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=PMZ:'>PMZ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LVJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Du, Z.]] | [[Category: Du, Z.]] | ||
| - | [[Category: James, T | + | [[Category: James, T L.]] |
| - | [[Category: Lind, K | + | [[Category: Lind, K E.]] |
[[Category: PMZ]] | [[Category: PMZ]] | ||
[[Category: complex (rna/drug)]] | [[Category: complex (rna/drug)]] | ||
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[[Category: transcriptional activation]] | [[Category: transcriptional activation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:48:51 2008'' |
Revision as of 11:48, 21 February 2008
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STRUCTURE OF TAR RNA COMPLEXED WITH A TAT-TAR INTERACTION NANOMOLAR INHIBITOR THAT WAS IDENTIFIED BY COMPUTATIONAL SCREENING
Overview
HIV-1 TAR RNA functions critically in viral replication by binding the transactivating regulatory protein Tat. We recently identified several compounds that experimentally inhibit the Tat-TAR interaction completely at a 100 nM concentration. We used computational screening of the 181,000-compound Available Chemicals Directory against the three-dimensional structure of TAR [1]. Here we report the NMR-derived structure of TAR complexed with acetylpromazine. This structure represents a new class of compounds with good bioavailability and low toxicity that bind with high affinity to TAR. NMR data unambiguously show that acetylpromazine binds only to the unique 5' bulge site to which the Tat protein binds. Specificity and affinity of binding are conferred primarily by a network of base stacking and hydrophobic interactions. Acetylpromazine alters the structure of free TAR less than Tat peptides and neomycin do.
About this Structure
1LVJ is a Protein complex structure of sequences from Human immunodeficiency virus 1 with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of TAR RNA complexed with a Tat-TAR interaction nanomolar inhibitor that was identified by computational screening., Du Z, Lind KE, James TL, Chem Biol. 2002 Jun;9(6):707-12. PMID:12079782
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