2ZZO

Crystal structure of the complex between GP41 fragment N36 and fusion inhibitor C34/S138A

Summary for 2ZZO

• Entry DOI: 10.2210/pdb2zzo/pdb
• Descriptor: Transmembrane protein (3 entities in total)
• Functional Keywords: hiv-1, gp41, viral protein-inhibitor complex, viral protein/inhibitor
• Cellular location: Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: P04578 P04578
• Total number of polymer chains: 2
• Total formula weight: 8414.46

Authors

Watabe, T.,Nakano, H.,Nakatsu, T.,Kato, H.,Fujii, N. (deposition date: 2009-02-20, release date: 2009-08-04, Last modification date: 2024-10-16)

Primary citation

Watabe, T.,Terakawa, Y.,Watanabe, K.,Ohno, H.,Nakano, H.,Nakatsu, T.,Kato, H.,Izumi, K.,Kodama, E.,Matsuoka, M.,Kitaura, K.,Oishi, S.,Fujii, N.
X-ray crystallographic study of an HIV-1 fusion inhibitor with the gp41 S138A substitution
J.Mol.Biol., 392:657-665, 2009

PubMed Abstract: The S138A substitution of fusion inhibitory peptides derived from the C-terminal heptad repeat (C-HR) of the human immunodeficiency virus type 1 (HIV-1) gp41 leads to enhanced binding affinity to the N-terminal heptad repeat (N-HR). As such, these peptides exhibit highly potent anti-HIV-1 activity. X-ray crystallographic analysis was performed to understand the effect of the substitution on binding affinity. The comparison of the native and S138A crystal structures indicated that the increase in the hydrophobicity of the S138A substitution may aid the stabilization of the N-HR/C-HR complex through additional hydrophobic contacts. Free-energy calculations suggest that the difference between the desolvation free energies of the C-HR-derived peptides with and without the S138A mutation dominates the observed difference in anti-HIV-1 activity.

PubMed: 19616557
DOI: 10.1016/j.jmb.2009.07.027

Experimental method

X-RAY DIFFRACTION (2.2 Å)