Conformation of the flavin adenine dinucleotide cofactor FAD in DNA-photolyase: A molecular dynamics study
Conformation of the flavin adenine dinucleotide cofactor FAD in DNA-photolyase: A molecular dynamics study
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DOI：
10.1007/s008940050133
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发表时间：
1998-01-01
影响因子：
2.2
通讯作者：
Rosch, N
中科院分区：
文献类型：
--
作者：
Hahn, J;Michel-Beyerle, ME;Rosch, N
为了深入了解光驱动的DNA修复的酶DNA光裂合酶，构象的光活性辅因子FAD，黄素腺嘌呤二核苷酸，已被研究的分子动力学模拟。相反，在气相中的FAD和在水中的MD程序产生各种“开放”的I-形以及“封闭”的U-形构象，FAD结合酶的计算基本上显示了一个单一的U-形构象的辅因子，到目前为止，这是唯一的携带FAD的蛋白质。这种U形构象的特征是FAD组分占据蛋白质表面中的口袋的相对侧，所述口袋为DNA上的缺陷嘧啶二聚体结构提供结合位点。事实上，计算的U形构象与DNA光裂合酶的X射线结构分析所揭示的构象非常接近。此外，模拟产生的光活性isoalloxazine部分的结合和形成的酶的结合腔的氨基酸的动力学的细节。
In order to gain insight into the light-driven repair of DNA by the enzyme DNA photolyase, the conformation of the photoactive cofactor FAD, a flavin adenine dinucleotide, has been studied by molecular dynamic simulations. In contrast to FAD in the gas phase and in water where the MD procedure yields various "open" I-shaped as well as "closed" U-shaped conformations, the calculations of FAD binding to the enzyme show essentially a single U-shaped conformation of this cofactor which, so far, is unique among FAD-carrying proteins. It is characteristic for this U-shaped conformation that the FAD components occupy opposite sides of the pocket in the surface of the protein which provides the binding site for the defect pyrimidine dimer structure on DNA. In fact, the calculated U-shaped conformation is very close to the one revealed by the X-ray structure analysis of DNA photolyase. Moreover, the simulations yield details on the binding of the photoactive isoalloxazine moiety and the dynamics of the amino acids forming the binding cavity of the enzyme.