1uts

Designed HIV-1 TAR Binding Ligand

spinqualitylabelsall models 1uts Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1uts is a 1 chain structure with sequence from Human immunodeficiency virus 1. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: P13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The targeting of RNA for the design of novel anti-viral compounds represents an area of vast potential. We have used NMR and computational methods to model the interaction of a series of synthetic inhibitors of the in vitro RNA binding activities of a peptide derived from the transcriptional activator protein, Tat, from human immunodeficiency virus type 1. Inhibition has been measured through the monitering of fluorescence resonance energy transfer between fluorescently labeled peptide and RNA components. A series of compounds containing a bi-aryl heterocycle as one of the three substituents on a benzylic scaffold, induce a novel, inactive TAR conformation by stacking between base-pairs at the site of a three-base bulge within TAR. The development of this series resulted in an enhancement in potency (with Ki < 100 nM in an in vitro assay) and the removal of problematic guanidinium moieties. Ligands from this series can act as inhibitors of Tat-induced transcription in a cell-free system. This study validates the drug design strategy of using a ligand to target the RNA receptor in a non-functional conformation. Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA.,Murchie AI, Davis B, Isel C, Afshar M, Drysdale MJ, Bower J, Potter AJ, Starkey ID, Swarbrick TM, Mirza S, Prescott CD, Vaglio P, Aboul-ela F, Karn J J Mol Biol. 2004 Feb 20;336(3):625-38. PMID:15095977 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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