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首页> 外文期刊>Journal of Molecular Biology >The NMR Solution Structure of Intestinal Fatly Acid-binding Protein Complexed with Palmitate: Application of a Novel Distance Geometry Algorithm
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The NMR Solution Structure of Intestinal Fatly Acid-binding Protein Complexed with Palmitate: Application of a Novel Distance Geometry Algorithm

机译：棕榈酸酯结合的肠脂肪酸结合蛋白的NMR溶液结构：新型距离几何算法的应用

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The three-dimensional solution structure of rat intestinal fatty acid-binding protein (I-FABP) complexed with palmitate has been determined using multidimensional triple-resonance NMR methods. The structure is based on 3889 conformational restraints derived mostly from 3-D ~(13)C- and ~(15)N-resolved nuclear Overhauser (NOESY) experiments. The 3-D NOESY dala for this 15.4 kDa complex contained an average of nine possible interpretations per cross-peak. To circumvent this ambiguity, an eight-stage iterative procedure was employed to gradually interpret and introduce unambiguous distance restraints during subsequent rounds of structure calculations. The first stage of this procedure relied critically upon an initial structural model based on the consensus ~1H/~(13)C chemical shift-derived secondary structure and a set of symmetry-checked restraints derived from the 3-D ~(13)C-resolved NOESY spectrum. The structures were calculated using DISTGEOM, a program that implements a novel distance geometry algorithm with pairwise Gaussian metrication. A central feature of this algorithm is the use of an iteratively optimized Gaussian distribution for the selection of trial distances, which overcomes the tendency of metrization to produce crushed structures.In addition, this algorithm randomly selects pairwise elements of the distance matrix, which results in an improved sampling of conformational space for a given computational effort. The final family of 20 distance geometry/simulated annealing structuresexhibited an average pairwise C~a root-mean-square deviation of 0.98 A, and their stereochemical quality, as assessed by PROCHECK, was comparable to that of 2.5 A X-ray crystal structures. The NMR structure was compared with the X-ray crystal structureof the same ligand/protein complex and was found to be essentially identical within the precision of the results. The NMR structure was also compared with that of the palmitate complex with bovine heart FABP, which shares 30% sequence identity with rat I-FABP. The overall folds were the same, but differences were noted with respect to the presence or absence of apparent conformational heterogeneity and the location and conformation of the bound fatty acid.
机译：已使用多维三共振NMR方法确定了与棕榈酸酯复合的大鼠肠道脂肪酸结合蛋白（I-FABP）的三维溶液结构。该结构基于3889个构象约束，这些构象约束主要来自3-D〜（13）C-和〜（15）N分辨核Overhauser（NOESY）实验。这个15.4 kDa的复合物的3-D NOESY dala每个交叉峰平均包含九种可能的解释。为了避免这种歧义，在随后的几轮结构计算中，采用了八阶段迭代过程来逐步解释和引入明确的距离约束。此过程的第一阶段主要依赖于基于共有〜1H /〜（13）C化学位移衍生的二级结构的初始结构模型以及从3-D〜（13）C导出的一组对称检查的约束解析的NOESY光谱。使用DISTGEOM计算结构，DISTGEOM是一个程序，该程序实现了具有成对的高斯度量的新型距离几何算法。该算法的主要特点是使用迭代优化的高斯分布来选择试验距离，从而克服了金属化产生挤压结构的趋势;此外，该算法随机选择距离矩阵的成对元素，从而得出对于给定的计算工作量，改进的构象空间采样。最终的20种距离几何结构/模拟退火结构族的平均成对C〜均方根偏差为0.98 A，通过PROCHECK评估，其立体化学质量与2.5 A X射线晶体结构相当。将NMR结构与相同配体/蛋白质复合物的X射线晶体结构进行了比较，发现在结果的精度范围内基本相同。 NMR结构也与具有牛心FABP的棕榈酸酯复合物的结构进行了比较，后者与大鼠I-FABP具有30％的序列同一性。总体折叠是相同的，但是在明显的构象异质性的存在与否以及结合的脂肪酸的位置和构象方面注意到差异。

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