2kx5
From Proteopedia
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[[Image:2kx5.png|left|200px]] | [[Image:2kx5.png|left|200px]] | ||
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{{STRUCTURE_2kx5| PDB=2kx5 | SCENE= }} | {{STRUCTURE_2kx5| PDB=2kx5 | SCENE= }} | ||
===Recognition of HIV TAR RNA by peptide mimetic of Tat protein=== | ===Recognition of HIV TAR RNA by peptide mimetic of Tat protein=== | ||
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{{ABSTRACT_PUBMED_20724442}} | {{ABSTRACT_PUBMED_20724442}} | ||
==About this Structure== | ==About this Structure== | ||
| - | [[2kx5]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KX5 OCA]. | + | [[2kx5]] is a 2 chain structure of [[Tat protein]]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KX5 OCA]. |
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| + | ==See Also== | ||
| + | *[[Tat protein|Tat protein]] | ||
==Reference== | ==Reference== | ||
| - | <ref group="xtra">PMID: | + | <ref group="xtra">PMID:020724442</ref><references group="xtra"/> |
[[Category: Davidson, A.]] | [[Category: Davidson, A.]] | ||
[[Category: Patora-Komisarska, K.]] | [[Category: Patora-Komisarska, K.]] | ||
[[Category: Robinson, J.]] | [[Category: Robinson, J.]] | ||
[[Category: Varani, G.]] | [[Category: Varani, G.]] | ||
| + | [[Category: Hiv-1 tar]] | ||
| + | [[Category: Immunodeficiency virus]] | ||
| + | [[Category: Rna binding protein-rna complex]] | ||
| + | [[Category: Rna recognition]] | ||
| + | [[Category: Tar rna]] | ||
| + | [[Category: Tat]] | ||
Revision as of 09:17, 26 July 2012
Contents |
Recognition of HIV TAR RNA by peptide mimetic of Tat protein
The pharmacological disruption of the interaction between the HIV Tat protein and its cognate transactivation response RNA (TAR) would generate novel anti-viral drugs with a low susceptibility to drug resistance, but efforts to discover ligands with sufficient potency to warrant pharmaceutical development have been unsuccessful. We have previously described a family of structurally constrained beta-hairpin peptides that potently inhibits viral growth in HIV-infected cells. The nuclear magnetic resonance (NMR) structure of an inhibitory complex revealed that the peptide makes intimate contacts with the 3-nt bulge and the upper helix of the RNA hairpin, but that a single residue contacts the apical loop where recruitment of the essential cellular co-factor cyclin T(1) occurs. Attempting to extend the peptide to form more interactions with the RNA loop, we examined a library of longer peptides and achieved >6-fold improvement in affinity. The structure of TAR bound to one of the extended peptides reveals that the peptide slides down the major groove of the RNA, relative to our design, in order to maintain critical interactions with TAR. These conserved contacts involve three amino acid side chains and identify critical interaction points required for potent and specific binding to TAR RNA. They constitute a template of essential interactions required for inhibition of this RNA.
Essential structural requirements for specific recognition of HIV TAR RNA by peptide mimetics of Tat protein., Davidson A, Patora-Komisarska K, Robinson JA, Varani G, Nucleic Acids Res. 2010 Aug 19. PMID:20724442
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2kx5 is a 2 chain structure of Tat protein. Full experimental information is available from OCA.
See Also
Reference
- Davidson A, Patora-Komisarska K, Robinson JA, Varani G. Essential structural requirements for specific recognition of HIV TAR RNA by peptide mimetics of Tat protein. Nucleic Acids Res. 2010 Aug 19. PMID:20724442 doi:10.1093/nar/gkq713
