首页> 外国专利> CRYSTAL STRUCTURE OF BIFUNCTIONAL TRANSGLYCOSYLASE PBP1B FROM E. COLI AND INHIBITORS THEREOF

CRYSTAL STRUCTURE OF BIFUNCTIONAL TRANSGLYCOSYLASE PBP1B FROM E. COLI AND INHIBITORS THEREOF

机译:大肠杆菌的功能性双糖苷酶PBP1B的晶体结构及其抑制剂

摘要

Crystal structure at 2.16 Å resolution of full-length Escherichia coli penicillin-binding protein 1b (PBP1b) in complex with its inhibitor moenomycin, is provided. 3D structures of amino acid residues involved in moenomycin binding and transglycosylation activity are identified. Binding sites for peptidoglycan synthesis inhibitors comprising amino acid residues from transglycosylase (TG), UvrB domain 2 homolog (UB2H) and transmembrane (TM) domains of PBP1b are identified at atomic level resolution. Rational drug design, based on the atomic coordinates, are disclosed. Methods for screening for antibiotics using anisotropic binding and transglycosylase inhibitor assays and novel antibiotics based on the screening assays are provided.
机译:提供了全长2.16埃分辨率的青霉素结合蛋白青霉素结合蛋白1b(PBP1b)及其抑制剂莫能霉素的晶体结构。确定了与莫诺霉素结合和转糖基化活性有关的氨基酸残基的3D结构。以原子水平的分辨率鉴定了肽聚糖合成抑制剂的结合位点,所述抑制剂包含PBP1b的转糖基酶(TG),UvrB结构域2同源物(UB2H)和跨膜(TM)结构域的氨基酸残基。公开了基于原子坐标的合理药物设计。提供了使用各向异性结合和转糖基酶抑制剂试验筛选抗生素的方法,以及基于筛选试验的新型抗生素。

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