The Structure of a Transient Complex of a Nonribosomal Peptide Synthetase and a Cytochrome P450 Monooxygenase
The Structure of a Transient Complex of a Nonribosomal Peptide Synthetase and a Cytochrome P450 Monooxygenase
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DOI：
10.1002/anie.201404977
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发表时间：
2014-08-04
影响因子：
16.6
通讯作者：
Cryle, Max J.
中科院分区：
文献类型：
--
作者：
Haslinger, Kristina;Brieke, Clara;Cryle, Max J.
研究非核糖体肽合成酶（NRPS），次级代谢产物的主要来源，和关键的外部修饰酶之间的相互作用是一项具有挑战性的任务，因为所涉及的相互作用往往是短暂的性质。通过应用一系列合成的杂合物型化合物，产生了适合于结构分析的稳定复合物，用于这样的剪裁酶和NRPS结构域。研究的复合物包括NRPS肽基载体蛋白（PCP）域结合的细胞色素P450酶，这是至关重要的β-羟基化的氨基酸前体的生物合成中的环状缩肽斯凯拉霉素的提供。结构表明，复合物的形成是由疏水相互作用，它的存在可以通过控制PCP结构，使多个高度相似的PCP结构域之间的选择性的微小改变。
Studying the interplay between nonribosomal peptide synthetases (NRPS), a major source of secondary metabolites, and crucial external modifying enzymes is a challenging task since the interactions involved are often transient in nature. By applying a range of synthetic inhibitor-type compounds, a stabilized complex appropriate for structural analysis was generated for such a tailoring enzyme and an NRPS domain. The complex studied comprises an NRPS peptidyl carrier protein (PCP) domain bound to the Cytochrome P450 enzyme that is crucial for the provision of beta-hydroxylated amino acid precursors in the biosynthesis of the cyclic depsipeptide skyllamycin. The structure reveals that complex formation is governed by hydrophobic interactions, the presence of which can be controlled through minor alterations in PCP structure that enable selectivity amongst multiple highly similar PCP domains.