2FXD

X-ray crystal structure of HIV-1 protease IRM mutant complexed with atazanavir (BMS-232632)

2FXD の概要

• エントリーDOI: 10.2210/pdb2fxd/pdb
• 関連するPDBエントリー: 2FXE
• 分子名称: pol protein, SULFATE ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: human immunodeficiency virus (hiv), hiv-1 protease, reyataz, atazanavir, bms-232632, hydrolase
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22379.32

構造登録者

Klei, H.E.,Sheriff, S. (登録日: 2006-02-04, 公開日: 2007-02-20, 最終更新日: 2023-08-30)

主引用文献

Klei, H.E.,Kish, K.,Lin, P.F.,Guo, Q.,Friborg, J.,Rose, R.E.,Zhang, Y.,Goldfarb, V.,Langley, D.R.,Wittekind, M.,Sheriff, S.
X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir.
J.Virol., 81:9525-9535, 2007

PubMed Abstract: Atazanavir, which is marketed as REYATAZ, is the first human immunodeficiency virus type 1 (HIV-1) protease inhibitor approved for once-daily administration. As previously reported, atazanavir offers improved inhibitory profiles against several common variants of HIV-1 protease over those of the other peptidomimetic inhibitors currently on the market. This work describes the X-ray crystal structures of complexes of atazanavir with two HIV-1 protease variants, namely, (i) an enzyme optimized for resistance to autolysis and oxidation, referred to as the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant of the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors, referred to as the inhibitor-resistant mutant. In these two complexes, atazanavir adopts distinct bound conformations in response to the V82F substitution, which may explain why this substitution, at least in isolation, has yet to be selected in vitro or in the clinic. Because of its nearly symmetrical chemical structure, atazanavir is able to make several analogous contacts with each monomer of the biological dimer.

PubMed: 17537865
DOI: 10.1128/JVI.02503-05

実験手法

X-RAY DIFFRACTION (1.6 Å)