Structure-activity based study of the Smac-binding pocket within the BIR3 domain of XIAP.
Structure-activity based study of the Smac-binding pocket within the BIR3 domain of XIAP.
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DOI：
10.1016/j.bmc.2007.02.010
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发表时间：
2007-04
影响因子：
3.5
通讯作者：
A. D. Wist;L. Gu;S. Riedl;Yigong Shi;G. Mclendon
中科院分区：
文献类型：
--
作者：
A. D. Wist;L. Gu;S. Riedl;Yigong Shi;G. Mclendon
设计并合成了一系列含有Smac-XIAP结合基序的小肽模拟物，取代了含有Smac-XIAP结合基序的四肽中潜在不稳定的N-末端肽键。两个Smac模拟物以中等亲和力结合到XIAP的BIR3结构域，其中一个在细胞中表现出比Smac多肽更高的活性。对BIR3-XIAP与Smac多肽和模拟多肽形成的复合物的结构进行了解析和分析，以阐明BIR3-XIAP中Smac结合域周围的构效关系。
A small series of peptide mimics was designed and synthesized to contain a heterocyclic ring in place of the potentially labile N-terminal peptide bond of the tetrapeptide containing the Smac-XIAP-binding motif. Two Smac mimics were shown to bind to the BIR3 domain of XIAP with moderate affinity and one displayed increased activity in cells relative to the Smac peptides. The structures of BIR3-XIAP in complex with a Smac peptide and a peptide mimic were solved and analyzed to elucidate the structure–activity relationship surrounding the Smac-binding domain within BIR3-XIAP.