2ns4
From Proteopedia
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| - | [[Image:2ns4.gif|left|200px]] | + | [[Image:2ns4.gif|left|200px]] |
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| - | '''Solution structure of a Beta-Hairpin Peptidomimetic Inhibitor of the BIV Tat-Tar Interaction''' | + | {{Structure |
| + | |PDB= 2ns4 |SIZE=350|CAPTION= <scene name='initialview01'>2ns4</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''Solution structure of a Beta-Hairpin Peptidomimetic Inhibitor of the BIV Tat-Tar Interaction''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2NS4 is a [ | + | 2NS4 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NS4 OCA]. |
==Reference== | ==Reference== | ||
| - | Structure-guided peptidomimetic design leads to nanomolar beta-hairpin inhibitors of the Tat-TAR interaction of bovine immunodeficiency virus., Athanassiou Z, Patora K, Dias RL, Moehle K, Robinson JA, Varani G, Biochemistry. 2007 Jan 23;46(3):741-51. PMID:[http:// | + | Structure-guided peptidomimetic design leads to nanomolar beta-hairpin inhibitors of the Tat-TAR interaction of bovine immunodeficiency virus., Athanassiou Z, Patora K, Dias RL, Moehle K, Robinson JA, Varani G, Biochemistry. 2007 Jan 23;46(3):741-51. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17223695 17223695] |
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Moehle, K.]] | [[Category: Moehle, K.]] | ||
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[[Category: nmr]] | [[Category: nmr]] | ||
[[Category: peptide structure]] | [[Category: peptide structure]] | ||
| - | [[Category: | + | [[Category: peptidomimetic]] |
[[Category: rna recognition]] | [[Category: rna recognition]] | ||
[[Category: tar rna]] | [[Category: tar rna]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:50:22 2008'' |
Revision as of 15:50, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
Solution structure of a Beta-Hairpin Peptidomimetic Inhibitor of the BIV Tat-Tar Interaction
Overview
The Tat protein of immunodeficiency viruses is the main activator of viral gene expression. By binding specifically to its cognate site, the transactivator response element (TAR), Tat mediates a strong induction of the production of all viral transcripts. In seeking a new chemical solution to inhibiting viral protein-RNA interactions, we recently identified inhibitors of the viral Tat protein from the bovine immunodeficiency virus (BIV) using conformationally constrained beta-hairpin peptidomimetics. We identified a micromolar ligand, called BIV2, and the structure of its complex with BIV TAR was determined by NMR. In this work, we demonstrate that this chemistry can rapidly yield highly potent and selective ligands. On the basis of the structure, we synthesized and assayed libraries of mutant peptidomimetics. Remarkably, we were able in just a few rounds of design and synthesis to discover nanomolar inhibitors of the Tat-TAR interaction in BIV that selectively bind the BIV TAR RNA compared to RNA structures as closely related as the HIV-1 TAR or RRE elements. The molecular recognition principles developed in this study have been exploited in discovering related peptidomimetic inhibitors of the Tat-TAR interaction in HIV-1.
About this Structure
2NS4 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Structure-guided peptidomimetic design leads to nanomolar beta-hairpin inhibitors of the Tat-TAR interaction of bovine immunodeficiency virus., Athanassiou Z, Patora K, Dias RL, Moehle K, Robinson JA, Varani G, Biochemistry. 2007 Jan 23;46(3):741-51. PMID:17223695
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