2L6E

NMR Structure of the monomeric mutant C-terminal domain of HIV-1 Capsid in complex with stapled peptide Inhibitor

「2K1C」から置き換えられました

2L6E の概要

• エントリーDOI: 10.2210/pdb2l6e/pdb
• NMR情報: BMRB: 17307
• 関連するBIRD辞書のPRD_ID: PRD_000966
• 分子名称: Capsid protein p24, NYAD-13 stapled peptide inhibitor (2 entities in total)
• 機能のキーワード: protein-stapled peptide complex, viral protein - peptide inhibitor complex, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• 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): P35963
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13234.22

構造登録者

Bhattacharya, S.,Zhang, H.,Debnath, A.K.,Cowburn, D. (登録日: 2010-11-18, 公開日: 2010-12-29, 最終更新日: 2024-10-16)

主引用文献

Bhattacharya, S.,Zhang, H.,Debnath, A.K.,Cowburn, D.
Solution structure of a hydrocarbon stapled peptide inhibitor in complex with monomeric C-terminal domain of HIV-1 capsid.
J.Biol.Chem., 283:16274-16278, 2008

PubMed Abstract: The human immunodeficiency virus type 1 (HIV-1) capsid protein plays a critical role in virus core particle assembly and is an important target for novel therapeutic strategies. In a previous study, we characterized the binding affinity of a hydrocarbon stapled helical peptide, NYAD-1, for the capsid protein (K(d) approximately 1 mum) and demonstrated its ability to penetrate the cell membrane (Zhang, H., Zhao, Q., Bhattacharya, S., Waheed, A. A., Tong, X., Hong, A., Heck, S., Goger, M., Cowburn, D., Freed, E. O., and Debnath, A. K. (2008) J. Mol. Biol. 378, 565-580). In cell-based assays, NYAD-1 colocalized with the Gag polyprotein during traffic to the plasma membrane and disrupted the formation of mature and immature virus particles in vitro systems. Here, we complement the cellular and biochemical data with structural characterization of the interactions between the capsid and a soluble peptide analogue, NYAD-13. Solution NMR methods were used to determine a high resolution structure of the complex between the inhibitor and a monomeric form of the C-terminal domain of the capsid protein (mCA-CTD). The intermolecular interactions are mediated by the packing of hydrophobic side chains at the buried interface and unperturbed by the presence of the olefinic chain on the solvent-exposed surface of the peptide. The results of the structural analysis provide valuable insight into the determinants for high affinity and selective inhibitors for HIV-1 particle assembly.

PubMed: 18417468
DOI: 10.1074/jbc.C800048200

実験手法

SOLUTION NMR