2FJX

RT29 bound to D(CTTGAATGCATTCAAG) in complex with MMLV RT catalytic fragment

2FJX の概要

• エントリーDOI: 10.2210/pdb2fjx/pdb
• 関連するPDBエントリー: 2FJV 2FJW
• 分子名称: 5'-D(*CP*TP*TP*GP*AP*AP*TP*G)-3', 5'-D(P*CP*AP*TP*TP*CP*AP*AP*G)-3', Reverse transcriptase, ... (5 entities in total)
• 機能のキーワード: mmlv rt, protein-dna complex, water-mediated interaction, dna-drug complex, rt29, transferase-dna complex, transferase/dna
• 由来する生物種: Moloney murine leukemia virus
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor (Potential). Matrix protein p15: Virion (Potential). Capsid protein p30: Virion (Potential). Nucleocapsid protein p10: Virion (Potential): P03355
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 34156.94

構造登録者

Goodwin, K.D.,Georgiadis, M.M. (登録日: 2006-01-03, 公開日: 2006-06-27, 最終更新日: 2024-02-14)

主引用文献

Goodwin, K.D.,Lewis, M.A.,Tanious, F.A.,Tidwell, R.R.,Wilson, W.D.,Georgiadis, M.M.,Long, E.C.
A High-Throughput, High-Resolution Strategy for the Study of Site-Selective DNA Binding Agents: Analysis of a "Highly Twisted" Benzimidazole-Diamidine.
J.Am.Chem.Soc., 128:7846-7854, 2006

PubMed Abstract: A general strategy for the rapid structural analysis of DNA binding ligands is described as it was applied to the study of RT29, a benzimidazole-diamidine compound containing a highly twisted diphenyl ether linkage. By combining the existing high-throughput fluorescent intercalator displacement (HT-FID) assay developed by Boger et al. and a high-resolution (HR) host-guest crystallographic technique, a system was produced that was capable of determining detailed structural information pertaining to RT29-DNA interactions within approximately 3 days. Our application of the HT/HR strategy immediately revealed that RT29 has a preference for 4-base pair (bp), A.T-rich sites (AATT) and a similar tolerance and affinity for three A-T-bp sites (such as ATTC) containing a G.C bp. On the basis of these selectivities, oligonucleotides were designed and the host-guest crystallographic method was used to generate diffraction quality crystals. Analysis of the resulting crystal structures revealed that the diphenyl ether moiety of RT29 undergoes conformational changes that allow it to adopt a crescent shape that now complements the minor groove structure. The presence of a G.C bp in the RT29 binding site of ATTC did not overly perturb its interaction with DNA-the compound adjusted to the nucleobases that were available through water-mediated interactions. Our analyses suggest that the HT/HR strategy may be used to expedite the screening of novel minor groove binding compounds leading to a direct, HR structural determination.

PubMed: 16771498
DOI: 10.1021/ja0600936

実験手法

X-RAY DIFFRACTION (1.8 Å)