Dynamics of dehaloperoxidase-hemoglobin A derived from NMR relaxation spectroscopy and molecular dynamics simulation.
Dynamics of dehaloperoxidase-hemoglobin A derived from NMR relaxation spectroscopy and molecular dynamics simulation.
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DOI：
10.1016/j.jinorgbio.2018.01.006
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发表时间：
2018
影响因子：
3.9
通讯作者：
Jing Zhao;Mengjun Xue;Dorota Gudanis;H. Gracz;G. Findenegg;Z. Gdaniec;S. Franzen
中科院分区：
文献类型：
--
作者：
Jing Zhao;Mengjun Xue;Dorota Gudanis;H. Gracz;G. Findenegg;Z. Gdaniec;S. Franzen
脱卤过氧化物酶血红蛋白是第一个被鉴定具有生物相关氧化功能的血红蛋白，其中包括过氧化物酶、过氧化酶和氧化酶活性。在此，我们报告了一项使用异核核磁共振弛豫方法和分子动力学 (MD) 模拟对 DHP 的蛋白质主链动力学进行的研究，以解决蛋白质动力学在从一种功能切换到另一种功能中的作用。结果表明，DHP的主链螺旋区域和转角的平均有序参数分别为S2=0.87±0.03和S2=0.76±0.08。此外，DHP 主要是溶液中的单体，基于使用程序relax 中的长扩散张量模型计算的总翻滚相关时间τmis 9.49±1.65ns。许多氨基酸残基具有显着的Rexusing Lipari-Szabo无模型形式主义。这些包括 Lys3、Ile6、Leu13、Gln18、Arg32、Ser48、Met49、Thr56、Phe60、Arg69、Thr71Cys73、Ala77、Asn81、Gly95、Arg109、Phe115、Leu127 和 Met136，它们可能在微秒-毫秒时间尺度上经历缓慢的构象运动根据模型。当模型包含 >4 个拟合参数时应小心。使用programcaver3.0识别从MD模拟快照获得的DHP内的隧道，这与Xe结合位点的重要性一致，Xe结合位点位于隧道的中心交叉点。这些通道为 O2、H2O 和 H2O2 等小配体提供扩散路径，使其独立于底物和抑制剂（两者都是芳香族分子）的轨迹进入远端口袋。
Dehaloperoxidase-hemoglobin is the first hemoglobin identified with biologically-relevant oxidative functions, which include peroxidase, peroxygenase and oxidase activities. Herein we report a study of the protein backbone dynamics of DHP using heteronuclear NMR relaxation methods and molecular dynamics (MD) simulations to address the role of protein dynamics in switching from one function to another. The results show that DHP's backbone helical regions and turns have average order parameters of S2= 0.87 ± 0.03 and S2= 0.76 ± 0.08, respectively. Furthermore, DHP is primarily a monomer in solution based on the overall tumbling correlation timeτmis 9.49 ± 1.65 ns calculated using the prolate diffusion tensor model in the programrelax. A number of amino acid residues have significant Rexusing the Lipari-Szabo model-free formalism. These include Lys3, Ile6, Leu13, Gln18, Arg32, Ser48, Met49, Thr56, Phe60, Arg69, Thr71Cys73, Ala77, Asn81, Gly95, Arg109, Phe115, Leu127and Met136, which may experience slow conformational motions on the microseconds-milliseconds time scale according to the model. Caution should be used when the model contains >4 fitting parameters. The programcaver3.0was used to identify tunnels inside DHP obtained from MD simulation snapshots that are consistent with the importance of the Xe binding site, which is located at the central intersection of the tunnels. These tunnels provide diffusion pathways for small ligands such as O2, H2O and H2O2to enter the distal pocket independently of the trajectory of substrates and inhibitors, both of which are aromatic molecules.