1T05

HIV-1 reverse transcriptase crosslinked to template-primer with tenofovir-diphosphate bound as the incoming nucleotide substrate

1T05 の概要

• エントリーDOI: 10.2210/pdb1t05/pdb
• 関連するPDBエントリー: 1RTD 1T03
• 分子名称: oligonucleotide template, oligonucleotide primer, POL polyprotein, ... (8 entities in total)
• 機能のキーワード: hiv-1 reverse transcriptase, tenofovir, rt-dna complex, transferase-dna complex, transferase/dna
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03366 P04585
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 131187.19

構造登録者

Tuske, S.,Sarafianos, S.G.,Ding, J.,Arnold, E. (登録日: 2004-04-07, 公開日: 2004-05-11, 最終更新日: 2023-08-23)

主引用文献

Tuske, S.,Sarafianos, S.G.,Clark Jr., A.D.,Ding, J.,Naeger, L.K.,White, K.L.,Miller, M.D.,Gibbs, C.S.,Boyer, P.L.,Clark, P.,Wang, G.,Gaffney, B.L.,Jones, R.A.,Jerina, D.M.,Hughes, S.H.,Arnold, E.
Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir
Nat.Struct.Mol.Biol., 11:469-474, 2004

PubMed Abstract: Tenofovir, also known as PMPA, R-9-(2-(phosphonomethoxypropyl)adenine, is a nucleotide reverse transcriptase (RT) inhibitor. We have determined the crystal structures of two related complexes of HIV-1 RT with template primer and tenofovir: (i) a ternary complex at a resolution of 3.0 A of RT crosslinked to a dideoxy-terminated DNA with tenofovir-diphosphate bound as the incoming substrate; and (ii) a RT-DNA complex at a resolution of 3.1 A with tenofovir at the 3' primer terminus. The tenofovir nucleotide in the tenofovir-terminated structure seems to adopt multiple conformations. Some nucleoside reverse transcriptase inhibitors, including 3TC and AZT, have elements ('handles') that project beyond the corresponding elements on normal dNTPs (the 'substrate envelope'). HIV-1 RT resistance mechanisms to AZT and 3TC take advantage of these handles; tenofovir's structure lacks handles that could protrude through the substrate envelope to cause resistance.

PubMed: 15107837
DOI: 10.1038/nsmb760

実験手法

X-RAY DIFFRACTION (3 Å)