X-ray crystallographic study of an HIV-1 fusion inhibitor with the gp41 S138A substitution.
X-ray crystallographic study of an HIV-1 fusion inhibitor with the gp41 S138A substitution.
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DOI：
10.1016/j.jmb.2009.07.027
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发表时间：
2009-09
影响因子：
5.6
通讯作者：
T. Watabe;Y. Terakawa;Kentaro Watanabe;H. Ohno;H. Nakano;T. Nakatsu;H. Kato;Kazuki Izumi;E. Kodama;M. Matsuoka;K. Kitaura;S. Oishi;N. Fujii
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文献类型：
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作者：
T. Watabe;Y. Terakawa;Kentaro Watanabe;H. Ohno;H. Nakano;T. Nakatsu;H. Kato;Kazuki Izumi;E. Kodama;M. Matsuoka;K. Kitaura;S. Oishi;N. Fujii
从人类免疫缺陷病毒1型（HIV-1） gp41的c端七肽重复序列（C-HR）衍生的融合抑制肽的S138A取代导致与n端七肽重复序列（N-HR）的结合亲和力增强。因此，这些肽表现出高度有效的抗hiv -1活性。x射线晶体学分析了解取代对结合亲和力的影响。对S138A和S138A晶体结构的比较表明，S138A取代物的疏水性增加可能有助于通过增加疏水接触来稳定N-HR/C-HR配合物。自由能计算表明，携带和不携带S138A突变的c - hr衍生肽的脱溶自由能之间的差异主导了观察到的抗hiv -1活性差异。
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.