An open and a closed conformation of a surface loop in PhaZ7 extracellular poly(3‐hydroxybutyrate) depolymerase were identified in two high‐resolution crystal structures of a PhaZ7 Y105E mutant. Molecular dynamics (MD) simulations revealed high root mean square fluctuations (RMSF) of the 281–295 loop, in particular at residue Asp289 (RMSF 7.62 Å). Covalent docking between a 3‐hydroxybutyric acid trimer and the catalytic residue Ser136 showed that the binding energy of the substrate is significantly more favorable in the open loop conformation compared to that in the closed loop conformation. MD simulations with the substrate covalently bound depicted 1 Å RMSF higher values for the residues 281–295 in comparison to the apo (substrate‐free) form. In addition, the presence of the substrate in the active site enhanced the ability of the loop to adopt a closed form. Taken together, the analysis suggests that the flexible loop 281–295 of PhaZ7 depolymerase can act as a lid domain to control substrate access to the active site of the enzyme. Proteins 2017; 85:1351–1361. © 2017 Wiley Periodicals, Inc.

中文翻译：

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晶体结构分析，共价对接和分子动力学计算揭示了PhaZ7 PHB解聚酶中的构象转换

在PhaZ7 Y105E突变体的两个高分辨率晶体结构中，发现了PhaZ7细胞外聚（3-羟基丁酸酯）解聚酶表面环的开环和闭环构型。分子动力学（MD）模拟揭示了281-295环的高均方根波动（RMSF），特别是在残基Asp289（RMSF 7.62Å）处。3-羟基丁酸三聚体和催化残基Ser136之间的共价对接表明，与闭环构型相比，开环构型中底物的结合能明显更有利。与底物共价结合的MD模拟显示，与apo（无底物）形式相比，残基281–295的RSF值高​​1Å。此外，活性位点中底物的存在增强了环采用封闭形式的能力。两者合计，分析表明PhaZ7解聚酶的柔性环281-295可以作为盖结构域，以控制底物对酶活性位点的访问。蛋白质2017; 85：1351–1361。©2017 Wiley Periodicals，Inc.