Beyond active site residues: overall structural dynamics control catalysis in flavin-containing and heme-containing monooxygenases
Beyond active site residues: overall structural dynamics control catalysis in flavin-containing and heme-containing monooxygenases
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DOI：
10.1016/j.sbi.2019.01.019
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发表时间：
2019-12-01
影响因子：
6.8
通讯作者：
Fraaije, Marco W.
中科院分区：
文献类型：
--
作者：
Furst, Maximilian J. L. J.;Fiorentini, Filippo;Fraaije, Marco W.
单加氧酶（MO）面临着有机靶标、氧和辅因子（最常见的是血红素或黄素）的挑战性反应。为了在空间和时间上正确地编排底物，MO进化出了各种各样的策略，这些策略涉及结构灵活性。除了经典的结构域和环运动，含黄素的MO的功能构象变化的黄素辅基和烟酰胺辅因子。随着类似的机制出现在各种子类中，它们的普遍性和参与选择性是有趣的问题。细胞色素P450 MO通常具有固有的可塑性，并且在整个结构中发生单个片段的大运动。由于这些复杂且通常不可预测的运动在很大程度上负责底物摄取，因此当在整个结构中随机突变残基时，这些酶的工程策略大多是成功的。
Monooxygenases (MOs) face the challenging reaction of an organic target, oxygen and a cofactor - most commonly heme or flavin. To correctly choreograph the substrates spatially and temporally, MOs evolved a variety of strategies, which involve structural flexibility. Besides classical domain and loop movements, flavin-containing MOs feature conformational changes of their flavin prosthetic group and their nicotinamide cofactor. With similar mechanisms emerging in various subclasses, their generality and involvement in selectivity are intriguing questions. Cytochrome P450 MOs are often inherently plastic and large movements of individual segments throughout the entire structure occur. As these complicated and often unpredictable movements are largely responsible for substrate uptake, engineering strategies for these enzymes were mostly successful when randomly mutating residues across the entire structure.