Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli
Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli
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DOI：
10.1073/pnas.0904030106
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发表时间：
2009-06-02
影响因子：
11.1
通讯作者：
Ma, Che
中科院分区：
文献类型：
--
作者：
Sung, Ming-Ta;Lai, Yen-Ting;Ma, Che
近年来，耐药细菌已经引起了严重的医疗问题，对新抗菌剂的需求是无可争议的。转糖基酶是细胞壁合成所必需的多结构域膜蛋白，是开发新抗生素的良好靶点。在这里，我们确定了X射线晶体结构的双功能转糖基酶青霉素结合蛋白1b（PBP 1b）从大肠杆菌在复杂的抑制剂默诺霉素到2.16埃的分辨率。除了转糖基酶和转肽酶结构域，我们的结构提供了一个完整的可视化这一重要的抗菌目标，并揭示了一个结构域的蛋白质-蛋白质相互作用和跨膜螺旋结构域的底物结合，酶的活性，和膜的方向。
Drug-resistant bacteria have caused serious medical problems in recent years, and the need for new antibacterial agents is undisputed. Transglycosylase, a multidomain membrane protein essential for cell wall synthesis, is an excellent target for the development of new antibiotics. Here, we determined the X-ray crystal structure of the bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from Escherichia coli in complex with its inhibitor moenomycin to 2.16-angstrom resolution. In addition to the transglycosylase and transpeptidase domains, our structure provides a complete visualization of this important antibacterial target, and reveals a domain for protein-protein interaction and a transmembrane helix domain essential for substrate binding, enzymatic activity, and membrane orientation.