Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity
Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity
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DOI：
10.1021/jm101625x
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发表时间：
2011-06-23
影响因子：
7.3
通讯作者：
Massey, Andrew J.
中科院分区：
文献类型：
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作者：
Macias, Alba T.;Williamson, Douglas S.;Massey, Andrew J.
78 kDa葡萄糖调节蛋白（Grp 78）是一种热休克蛋白（HSP），参与蛋白质折叠，在癌细胞增殖中发挥作用。结合腺苷衍生的抑制剂Grp 78的特征在于通过表面等离子体共振和等温滴定量热法。最有效的化合物为13种（VER-155008），K-D = 80 nM，14种K-D = 60 nM。Grp 78结合ATP，ADP 3，和腺苷衍生物10的X射线晶体结构显示Grp 78和同源蛋白质之间的结合位点的差异。
78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K-D = 80 nM and 14 with K-D = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.