Crystal Structure of an Archaeal Rad51 Homologue in Complex with a Metatungstate Inhibitor
Crystal Structure of an Archaeal Rad51 Homologue in Complex with a Metatungstate Inhibitor
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DOI：
10.1021/bi900832t
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发表时间：
2009-07-28
期刊：
影响因子：
2.9
通讯作者：
Luo, Yu
中科院分区：
文献类型：
--
作者：
Li, Yang;He, Yujiong;Luo, Yu
真核RadA与真核Rad51同源性很近（相似于40%的序列同一性）。这些重组酶促进同源单链和双链DNA底物之间的标志性链交换过程。这种DNA修复功能在癌细胞对化疗和放疗的抵抗中也起着关键作用。链交换过程的抑制可以使癌细胞对治疗性处理更敏感。我们发现偏钨酸盐是甲烷球菌RadA的有效抑制剂。钨簇在轴向DNA结合沟中结合RadA。这种聚阴离子物质似乎通过将蛋白质锁定在其非活性构象来抑制RadA。
Archaeal RadAs are close homologues of eukaryal Rad51s (similar to 40% sequence identities). These recombinases promote a hallmark strand exchange process between homologous single-stranded and double-stranded DNA substrates. This DNA-repairing function also plays a key role in cancer cells' resistance to chemo- and radiotherapy. Inhibition of the strand exchange process may render cancer cells more susceptible to therapeutic treatment. We found that metatungstate is a potent inhibitor of RadA from Methanococcus voltae. The tungsten cluster binds RadA in the axial DNA-binding groove. This polyanionic species appears to inhibit RadA by locking the protein in its inactive conformation.