Li Jun, Guan Xiaotao, Shaw Neil, Chen Weimin, Dong Yu, Xu Xiaoling, Li Xuemei, Rao Zihe
1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China [2].
1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China [2] Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin. 300071, China.
Sci Rep. 2014 Sep 23;4:6418. doi: 10.1038/srep06418.
Mycobacterium tuberculosis (Mtb) uses maltose-1-phosphate to synthesize α-glucans that make up the major component of its outer capsular layer. Maltose kinase (MaK) catalyzes phosphorylation of maltose. The molecular basis for this phosphorylation is currently not understood. Here, we describe the first crystal structure of MtbMaK refined to 2.4 Å resolution. The bi-modular architecture of MtbMaK reveals a remarkably unique N-lobe. An extended sheet protrudes into ligand binding pocket of an adjacent monomer and contributes residues critical for kinase activity. Structure of the complex of MtbMaK bound with maltose reveals that maltose binds in a shallow cavity of the C-lobe. Structural constraints permit phosphorylation of α-maltose only. Surprisingly, instead of a Gly-rich loop, MtbMaK employs 'EQS' loop to tether ATP. Notably, this loop is conserved across all MaK homologues. Structures of MtbMaK presented here unveil features that are markedly different from other kinases and support the scaffolding role proposed for this kinase.
结核分枝杆菌（Mtb）利用麦芽糖 - 1 - 磷酸来合成构成其外荚膜层主要成分的α - 葡聚糖。麦芽糖激酶（MaK）催化麦芽糖的磷酸化。目前尚不清楚这种磷酸化的分子基础。在此，我们描述了结核分枝杆菌麦芽糖激酶（MtbMaK）首个分辨率达到2.4 Å的晶体结构。MtbMaK的双模块结构显示出一个非常独特的N叶。一个延伸的片层突出到相邻单体的配体结合口袋中，并贡献了对激酶活性至关重要的残基。MtbMaK与麦芽糖结合的复合物结构表明，麦芽糖结合在C叶的一个浅腔中。结构限制仅允许α - 麦芽糖磷酸化。令人惊讶的是，MtbMaK不是使用富含甘氨酸的环，而是采用“EQS”环来连接ATP。值得注意的是，这个环在所有MaK同源物中都是保守的。本文展示的MtbMaK结构揭示了与其他激酶明显不同的特征，并支持了为该激酶提出的支架作用。
