3F4Z

Trimeric helix bundle formed by an alpha/beta-peptide derivative of the HIV gp41 CHR domain

3F4Z の概要

• エントリーDOI: 10.2210/pdb3f4z/pdb
• 関連するPDBエントリー: 3F4Y 3F50
• 分子名称: alpha/beta-peptide analogue of the HIV gp41 CHR domain, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total)
• 機能のキーワード: alpha/beta-peptide, helix bundle, viral protein
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 14523.65

構造登録者

Horne, W.S.,Gellman, S.H. (登録日: 2008-11-03, 公開日: 2009-09-15, 最終更新日: 2023-11-15)

主引用文献

Horne, W.S.,Johnson, L.M.,Ketas, T.J.,Klasse, P.J.,Lu, M.,Moore, J.P.,Gellman, S.H.
Structural and biological mimicry of protein surface recognition by alpha/beta-peptide foldamers
Proc.Natl.Acad.Sci.USA, 106:14751-14756, 2009

PubMed Abstract: Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining alpha- and beta-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that alpha/beta-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic alpha/beta-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived alpha-peptides. An optimized alpha/beta-peptide is far less susceptible to proteolytic degradation than is an analogous alpha-peptide. Our findings show how a two-stage design approach, in which sequence-based alpha-->beta replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.

PubMed: 19706443
DOI: 10.1073/pnas.0902663106

実験手法

X-RAY DIFFRACTION (2.1 Å)