Rimsa Vadim, Eadsforth Thomas C, Hunter William N
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Dec;69(Pt 12):1339-43. doi: 10.1107/S1744309113031448. Epub 2013 Nov 28.
Siah1 is an E3 ubiquitin ligase that contributes to proteasome-mediated degradation of multiple targets in key cellular processes and which shows promise as a therapeutic target in oncology. Structures of a truncated Siah1 bound to peptide-based inhibitors have been reported. Here, new crystallization conditions have allowed the determination of a construct encompassing dual zinc-finger subdomains and substrate-binding domains at significantly higher resolution. Although the crystals appear isomorphous, two structures present distinct states in which the spatial orientation of one zinc-finger subdomain differs with respect to the rest of the dimeric protein. Such a difference, which is indicative of conformational freedom, infers potential biological relevance related to recognition of binding partners. The crystallization conditions and improved models of Siah1 may aid future studies investigating Siah1-ligand complexes.
Siah1是一种E3泛素连接酶，它在关键细胞过程中有助于蛋白酶体介导的多个靶标的降解，并且作为肿瘤学中的治疗靶点显示出前景。已报道了与基于肽的抑制剂结合的截短型Siah1的结构。在这里，新的结晶条件使得能够以显著更高的分辨率确定包含双锌指亚结构域和底物结合结构域的构建体。尽管晶体看起来是同晶型的，但两种结构呈现出不同的状态，其中一个锌指亚结构域相对于二聚体蛋白的其余部分的空间取向不同。这种差异表明构象自由度，推断出与结合伴侣识别相关潜在生物学意义。Siah1的结晶条件和改进模型可能有助于未来研究Siah1-配体复合物。
