2L8H

Chemical probe bound to HIV TAR RNA

2L8H の概要

• エントリーDOI: 10.2210/pdb2l8h/pdb
• NMR情報: BMRB: 17408
• 分子名称: HIV TAR RNA, ARGININE, 4-methoxynaphthalen-2-amine (3 entities in total)
• 機能のキーワード: rna
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9655.98

構造登録者

Davidson, A.,Begley, D.,Lau, C.,Varani, G. (登録日: 2011-01-12, 公開日: 2011-03-23, 最終更新日: 2024-05-15)

主引用文献

Davidson, A.,Begley, D.W.,Lau, C.,Varani, G.
A Small-Molecule Probe Induces a Conformation in HIV TAR RNA Capable of Binding Drug-Like Fragments.
J.Mol.Biol., 410:984-996, 2011

PubMed Abstract: The HIV-1 transactivation response (TAR) element-Tat interaction is a potentially valuable target for treating HIV infection, but efforts to develop TAR-binding antiviral drugs have not yet yielded a successful candidate for clinical development. In this work, we describe a novel approach toward screening fragments against RNA that uses a chemical probe to target the Tat-binding region of TAR. This probe fulfills two critical roles in the screen: by locking the RNA into a conformation capable of binding other fragments, it simultaneously allows the identification of proximal binding fragments by ligand-based NMR. Using this approach, we have discovered six novel TAR-binding fragments, three of which were docked relative to the probe-RNA structure using experimental NMR restraints. The consistent orientations of functional groups in our data-driven docked structures and common electrostatic properties across all fragment leads reveal a surprising level of selectivity by our fragment-sized screening hits. These models further suggest linking strategies for the development of higher-affinity lead compounds for the inhibition of the TAR-Tat interaction.

PubMed: 21763501
DOI: 10.1016/j.jmb.2011.03.039

実験手法

SOLUTION NMR