Crystal structure of the termination module of a nonribosomal peptide synthetase
Crystal structure of the termination module of a nonribosomal peptide synthetase
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DOI：
10.1126/science.1159850
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发表时间：
2008-08-01
期刊：
影响因子：
56.9
通讯作者：
Marahiel, Mohamed A.
中科院分区：
文献类型：
--
作者：
Tanovic, Alan;Samel, Stefan A.;Marahiel, Mohamed A.
非核糖体肽合成酶（NRPSs）是一种模块化的多结构域酶，可作为催化复杂天然产物生物合成的装配线。在2.6埃分辨率下，对144千尔顿的枯草芽孢杆菌终止模SrfA- C的晶体结构进行了解析。SrfA- C的腺苷化和缩合结构域紧密结合形成一个催化平台，它们的活性位点在平台的同一侧。肽基载体蛋白结构域被灵活地拴在这个平台上，因此可以随着其载底物的4'-磷酸蚁氨酸臂在腺苷化结构域的活性位点和缩合结构域的供体侧之间移动。SrfA- C晶体结构对NRPSs的合理重新设计具有重要意义，可作为生产新型生物活性肽的手段。
Nonribosomal peptide synthetases ( NRPSs) are modular multidomain enzymes that act as an assembly line to catalyze the biosynthesis of complex natural products. The crystal structure of the 144- kilodalton Bacillus subtilis termination module SrfA- C was solved at 2.6 angstrom resolution. The adenylation and condensation domains of SrfA- C associate closely to form a catalytic platform, with their active sites on the same side of the platform. The peptidyl carrier protein domain is flexibly tethered to this platform and thus can move with its substrate- loaded 4'-phosphopantetheine arm between the active site of the adenylation domain and the donor side of the condensation domain. The SrfA- C crystal structure has implications for the rational redesign of NRPSs as a means of producing novel bioactive peptides.