Division of Structural Biology and Biochemistry, School of Biological Science, Nanyang Technological University, Singapore.
Proteins. 2012 Oct;80(10):2476-81. doi: 10.1002/prot.24146. Epub 2012 Jul 31.
Dengue remains one of the major public concerns as the virus eludes the immune response. Currently, no vaccines or antiviral therapeutics are available for dengue prevention or treatment. Immunosuppressive drug FK506 shows an antimalarial activity, and its molecular target, FK506-binding protein (FKBP), was identified in human Plasmodium parasites. Likewise, a conserved FKBP family protein has also been identified in Aedes aegypti (AaFKBP12), which is expected to play a similar role in the life cycle of Aedes aegypti, the primary vector of dengue virus infection. As FKBPs belong to a highly conserved class of immunophilin family and are involved in key biological regulations, they are considered as attractive pharmacological targets. In this study, we have determined the nuclear magnetic resonance solution structure of AaFKBP12, a novel FKBP member from Aedes aegypti, and presented its structural features, which may facilitate the design of potential inhibitory ligands against the dengue-transmitting mosquitoes.
登革热仍然是公众关注的主要问题之一，因为该病毒逃避了免疫反应。目前，尚无针对登革热预防或治疗的疫苗或抗病毒疗法。免疫抑制药物 FK506 具有抗疟活性，其分子靶标 FK506 结合蛋白 (FKBP) 在人类疟原虫中被鉴定出来。同样，在埃及伊蚊 (AaFKBP12) 中也鉴定出了一个保守的 FKBP 家族蛋白，预计它在埃及伊蚊的生命周期中发挥类似作用，埃及伊蚊是登革热病毒感染的主要媒介。由于 FKBPs 属于一类高度保守的免疫亲和素家族，参与关键的生物学调节，因此被认为是有吸引力的药理学靶点。在这项研究中，我们确定了来自埃及伊蚊的新型 FKBP 成员 AaFKBP12 的核磁共振溶液结构，并提出了其结构特征，这可能有助于设计针对传播登革热的蚊子的潜在抑制配体。
