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Sadashiva Maralinganadoddi Panchegowda Basappa NanjundaSwamy Shivananju Li Feng Manu Kanjoormana Aryan Sengottuvelan Murugan Prasanna Doddakunche Shivaramu Anilkumar Nirvanappa Chikkagundagal Sethi Gautam Sugahara Kazuyuki Rangappa Kanchugarakoppal Subbegowda 《BMC chemical biology》2012,12(1):1-11
Background
Nef is an HIV-1 accessory protein essential for viral replication and AIDS progression. Nef interacts with a multitude of host cell signaling partners, including members of the Src kinase family. Nef preferentially activates Hck, a Src-family kinase (SFK) strongly expressed in macrophages and other HIV target cells, by binding to its regulatory SH3 domain. Recently, we identified a series of kinase inhibitors that preferentially inhibit Hck in the presence of Nef. These compounds also block Nef-dependent HIV replication, validating the Nef-SFK signaling pathway as an antiretroviral drug target. Our findings also suggested that by binding to the Hck SH3 domain, Nef indirectly affects the conformation of the kinase active site to favor inhibitor association. 相似文献
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