HIV-1 整合酶对双相 DNA 结合的特异性影响。
Strain-specific effect on biphasic DNA binding by HIV-1 integrase.
机构信息
Department of Molecular Microbiology and Immunology.
Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
出版信息
AIDS. 2019 Mar 1;33(3):588-592. doi: 10.1097/QAD.0000000000002078.
Abstract
: The oligomerization of HIV-1 integrase onto DNA is not well understood. Here we show that HIV-1 integrase binds the DNA in biphasic (high-affinity and low-affinity) modes. For HIV-1 subtype B, the high-affinity mode is ∼100-fold greater than the low-affinity mode (Kd.DNA = 37 and 3400 nmol/l, respectively). The Kd.DNA values of patient-derived integrases containing subtype-specific polymorphisms were affected two- to four-fold, suggesting that polymorphisms may have an influence on effective-concentrations of inhibitors, as these inhibitors preferably bind to integrase-DNA complex.
摘要
HIV-1 整合酶与 DNA 的寡聚化作用尚未得到很好的理解。在这里，我们表明 HIV-1 整合酶以两相（高亲和力和低亲和力）模式结合 DNA。对于 HIV-1 亚型 B，高亲和力模式比低亲和力模式高约 100 倍（Kd.DNA=37 和 3400 nmol/l，分别）。包含亚型特异性多态性的患者衍生整合酶的 Kd.DNA 值受影响 2 至 4 倍，这表明多态性可能对抑制剂的有效浓度有影响，因为这些抑制剂优选与整合酶-DNA 复合物结合。
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