Structural and functional insights into a peptide bond-forming bidomain from a nonribosomal peptide synthetase
Structural and functional insights into a peptide bond-forming bidomain from a nonribosomal peptide synthetase
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DOI：
10.1016/j.str.2007.05.008
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发表时间：
2007-07-01
期刊：
影响因子：
5.7
通讯作者：
Essen, Lars-Oliver
中科院分区：
文献类型：
--
作者：
Samel, Stefan A.;Schoenafinger, Georg;Essen, Lars-Oliver
在1.8埃分辨率下测定了非核糖体酪氨酸合成酶TycC模块5和模块6的双结构域PCP-C的晶体结构。双结构域结构为v型缩合结构域，其峡谷状活性位点槽与其供体侧肽基载体蛋白（PCP）结构域相关联。PCP和缩氨酸成键缩合(C)结构域的相对排列使得活性位点相距50埃。因此，这种PCP-C结构代表了肽从供体- pcp转移到受体- pcp结构域之前的构象状态，这意味着在催化过程中存在PCP-C结构域相互作用的附加状态。此外，PCP-C发挥环化活性模式，模拟由C结构域催化的肽键形成。基于突变数据和活性位点残基的pK值分析，表明非核糖体肽键的形成依赖于静电相互作用，而不是一般的酸/碱催化。
The crystal structure of the bidomain PCP-C from modules 5 and 6 of the nonribosomal tyrocidine synthetase TycC was determined at 1.8 angstrom resolution. The bidomain structure reveals a V-shaped condensation domain, the canyon-like active site groove of which is associated with the preceding peptidyl carrier protein (PCP) domain at its donor side. The relative arrangement of the PCP and the peptide bond-forming condensation (C) domain places the active sites similar to 50 angstrom apart. Accordingly, this PCP-C structure represents a conformational state prior to peptide transfer from the donor-PCP to the acceptor-PCP domain, implying the existence of additional states of PCP-C domain interaction during catalysis. Additionally, PCP-C exerts a mode of cyclization activity that mimics peptide bond formation catalyzed by C domains. Based on mutational data and pK value analysis of active site residues, it is suggested that nonribosomal peptide bond formation depends on electrostatic interactions rather than on general acid/base catalysis.