Lim Kap, Zhang Hong, Tempczyk Aleksandra, Krajewski Wojciech, Bonander Nicklas, Toedt John, Howard Andrew, Eisenstein Edward, Herzberg Osnat
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, MD 20850, USA.
Proteins. 2003 Apr 1;51(1):56-67. doi: 10.1002/prot.10323.
The crystal structures of YibK from Haemophilus influenzae (HI0766) have been determined with and without bound cofactor product S-adenosylhomocysteine (AdoHcy) at 1.7 and 2.0 A resolution, respectively. The molecule adopts an alpha/beta fold, with a topology that differs from that of the classical methyltransferases. Most notably, HI0766 contains a striking knot that forms the binding crevice for the cofactor. The knot formation is correlated with an alternative arrangement of the secondary structure units compared with the classical methyltransferases. Two loop regions undergo conformational changes upon AdoHcy binding. In contrast to the extended conformation of the cofactor seen in the classical methyltransferase structures, AdoHcy binds to HI0766 in a bent conformation. HI0766 and its close sequence relatives are all shorter versions of the more remotely related rRNA/tRNA methyltransferases of the spoU sequence family. We propose that the spoU sequence family contains the same core domain for cofactor binding as HI0766 but has an additional domain for substrate binding. The substrate-binding domain is absent in HI0766 sequence family and may be provided by another Haemophilus influenzae partner protein, which is yet to be identified.
分别在1.7埃和2.0埃分辨率下测定了来自流感嗜血杆菌（HI0766）的YibK在结合和未结合辅因子产物S-腺苷同型半胱氨酸（AdoHcy）时的晶体结构。该分子采用α/β折叠，其拓扑结构与经典甲基转移酶不同。最值得注意的是，HI0766含有一个显著的结，形成了辅因子的结合裂隙。与经典甲基转移酶相比，结的形成与二级结构单元的另一种排列相关。两个环区域在AdoHcy结合时发生构象变化。与经典甲基转移酶结构中看到的辅因子的伸展构象相反，AdoHcy以弯曲构象与HI0766结合。HI0766及其紧密的序列亲属都是spoU序列家族中关系较远的rRNA/tRNA甲基转移酶的较短版本。我们提出，spoU序列家族与HI0766含有相同的辅因子结合核心结构域，但有一个额外的底物结合结构域。在HI0766序列家族中不存在底物结合结构域，可能由另一种尚未鉴定的流感嗜血杆菌伴侣蛋白提供。
