Molecular Enzymology Group, University of Groningen, Nijenborgh 4, 9747AG, Groningen, The Netherlands.
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 1, 27100, Pavia, Italy.
Curr Opin Struct Biol. 2019 Dec;59:29-37. doi: 10.1016/j.sbi.2019.01.019. Epub 2019 Mar 2.
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.
单加氧酶（MOs）面临着将有机靶标、氧气和辅助因子（最常见的是血红素或黄素）正确组合的挑战。为了在空间和时间上正确编排底物，MOs 进化出了多种策略，其中涉及结构的灵活性。除了经典的结构域和环运动外，黄素结合 MOs 还具有黄素辅基和烟酰胺辅因子的构象变化。由于类似的机制在不同的亚类中出现，它们的普遍性和选择性参与是一个有趣的问题。细胞色素 P450 MOs 通常具有内在的可塑性，整个结构中的单个片段会发生大的运动。由于这些复杂且往往不可预测的运动在很大程度上负责底物的摄取，因此当在整个结构中随机突变残基时，这些酶的工程策略通常是成功的。
