2FCX

HIV-1 DIS kissing-loop in complex with neamine

2FCX の概要

• エントリーDOI: 10.2210/pdb2fcx/pdb
• 関連するPDBエントリー: 1XP7 1Y3S 2FCY 2FCZ 2FD0
• 分子名称: HIV-1 DIS RNA, POTASSIUM ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: hiv-1, rna, aminoglycoside, antibiotics
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15728.20

構造登録者

Ennifar, E.,Paillart, J.C.,Marquet, R.,Dumas, P. (登録日: 2005-12-13, 公開日: 2006-05-16, 最終更新日: 2024-02-14)

主引用文献

Ennifar, E.,Paillart, J.C.,Bodlenner, A.,Walter, P.,Weibel, J.-M.,Aubertin, A.-M.,Pale, P.,Dumas, P.,Marquet, R.
Targeting the dimerization initiation site of HIV-1 RNA with aminoglycosides: from crystal to cell.
Nucleic Acids Res., 34:2328-2339, 2006

PubMed Abstract: The kissing-loop complex that initiates dimerization of genomic RNA is crucial for Human Immunodeficiency Virus Type 1 (HIV-1) replication. We showed that owing to its strong similitude with the bacterial ribosomal A site it can be targeted by aminoglycosides. Here, we present its crystal structure in complex with neamine, ribostamycin, neomycin and lividomycin. These structures explain the specificity for 4,5-disubstituted 2-deoxystreptamine (DOS) derivatives and for subtype A and subtype F kissing-loop complexes, and provide a strong basis for rational drug design. As a consequence of the different topologies of the kissing-loop complex and the A site, these aminoglycosides establish more contacts with HIV-1 RNA than with 16S RNA. Together with biochemical experiments, they showed that while rings I, II and III confer binding specificity, rings IV and V are important for affinity. Binding of neomycin, paromomycin and lividomycin strongly stabilized the kissing-loop complex by bridging the two HIV-1 RNA molecules. Furthermore, in situ footprinting showed that the dimerization initiation site (DIS) of HIV-1 genomic RNA could be targeted by these aminoglycosides in infected cells and virions, demonstrating its accessibility.

PubMed: 16679451
DOI: 10.1093/nar/gkl317

実験手法

X-RAY DIFFRACTION (2 Å)