2L45

C-terminal zinc knuckle of the HIVNCp7 with DNA

2L45 の概要

• エントリーDOI: 10.2210/pdb2l45/pdb
• 関連するPDBエントリー: 2L44 2L46
• NMR情報: BMRB: 17229
• 分子名称: C-TERMINAL ZINC KNUCLE OF THE HIV-NCP7, DNA (5'-D(P*TP*AP*CP*GP*CP*C)-3'), ZINC ION (3 entities in total)
• 機能のキーワード: ncp7, hiv, platinum, viral protein-dna complex, viral protein/dna
• 由来する生物種: HUMAN IMMUNODEFICIENCY VIRUS 1 (HIV-1)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 4065.21

構造登録者

Quintal, S.,Viegas, A.,Cabrita, E.,Farrell, N.,Erhardt, S. (登録日: 2010-10-01, 公開日: 2011-12-14, 最終更新日: 2024-05-01)

主引用文献

Quintal, S.,Viegas, A.,Erhardt, S.,Cabrita, E.J.,Farrell, N.P.
Platinated DNA affects zinc finger conformation. Interaction of a platinated single-stranded oligonucleotide and the C-terminal zinc finger of nucleocapsid protein HIVNCp7.
Biochemistry, 51:1752-1761, 2012

PubMed Abstract: This paper describes for the first time the intimate molecular details of the association between a platinated oligonucleotide and a zinc finger peptide. Site-specific platination of the guanine in a single-stranded hexanucleotide gave {[Pt(dien)d(5'-TACGCC-3')], Pt(dien)(6-mer)} (II) characterized by mass spectrometry and (1)H nuclear magnetic resonance (NMR) spectroscopy. The work extends the study of platinum-nucleobase complex-zinc finger interactions using small molecules such as [Pt(dien)(9-EtGua)](2+) (I). The structure of the (34-52) C-terminal finger of HIV nucleocapsid protein HIVNCp7 (ZF1) was characterized by (1)H NMR spectroscopy and compared with that of the N-terminal single finger and the two-finger "intact" NCp7. Interaction of II with ZF1 results in significant changes in comparison to the "free" uncomplexed hexanucleotide; the major changes occurring for Trp37 resonances that are broadened and moved upfield, and other major shifts are for Gln45 (Hε21, Hγ3, Qβ), Met46 (NH, Hγ2), Lys47 (NH, Qγ), and Glu50 (Hγ2, Hγ3). The Zn-Cys/His chemical shifts show only marginal deviations. The solution structures of ZF1 and the 6-mer-ZF1 and II-ZF1 adducts were calculated from the nuclear Overhauser effect spectroscopy-derived distance constraints. The DNA position in the II-ZF1 adduct is completely different than in the absence of platinum. Major differences are the appearance of new Met46-Cyt6 H5 and Trp37-Cyt5 H5 contacts but severe weakening of the Trp37-Gua4 contact, attributed to the steric effects caused by Gua4 platination, accompanied by a change in the position of the aromatic ring. The results demonstrate the feasibility of targeting specific ZF motifs with DNA-tethered coordination compounds, such as Pt compounds and Co macrocycles, with implications for drug targetting and indeed the intimate mechanisms of DNA repair of platinated DNA.

PubMed: 22303928
DOI: 10.1021/bi201834g

実験手法

SOLUTION NMR