Identification of a Single Amino Acid Required for APOBEC3 Antiretroviral Cytidine Deaminase Activity

Identification of a Single Amino Acid Required for APOBEC3 Antiretroviral Cytidine Deaminase Activity
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DOI:
10.1128/jvi.00243-11
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发表时间:
2011-06-01
影响因子:
5.4
通讯作者:
Zheng, Yong-Hui
Zheng, Yong-Hui
中科院分区:
医学2区
文献类型:
--
作者:
Dang, Ying;Abudu, Aierken;Zheng, Yong-Hui

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在研究 APOBEC3 (A3) 抗人类免疫缺陷病毒 1 型(抗 HIV-1)机制期间,我们在 320 位(C320)发现了一个可破坏 A3DE 活性的半胱氨酸。该残基位于最近鉴定的 A3G 中的 DNA 结合域中。用 A3F (Y307) 中的相应酪氨酸替换 C320,可使 A3DE 的抗病毒活性提高 20 倍以上。相反,用半胱氨酸替换 A3F Y307 或将类似的半胱氨酸插入 A3B 或 A3G 会破坏 A3 的抗 HIV 活性。进一步研究发现 C320 显着降低 A3DE 催化活性。
During studies of APOBEC3 (A3) anti-human immunodeficiency virus type 1 (anti-HIV-1) mechanisms, we identified a single cysteine at position 320 (C320) that disrupts A3DE activity. This residue is located in the recently identified DNA binding domain in A3G. Replacing C320 with a corresponding tyrosine from A3F (Y307) increased A3DE antiviral activity more than 20-fold. Conversely, replacing A3F Y307 with a cysteine or inserting a similar cysteine into A3B or A3G disrupted the anti-HIV activity of A3. Further investigation uncovered that C320 significantly reduces A3DE catalytic activity.