THE SOLUTION CONFORMATIONS OF FERRICHROME AND DEFERRIFERRICHROME DETERMINED BY H-1-NMR SPECTROSCOPY AND COMPUTATIONAL MODELING
THE SOLUTION CONFORMATIONS OF FERRICHROME AND DEFERRIFERRICHROME DETERMINED BY H-1-NMR SPECTROSCOPY AND COMPUTATIONAL MODELING
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DOI：
10.1002/bip.360300303
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发表时间：
1990-01-01
期刊：
影响因子：
2.9
通讯作者：
LLINAS, M
中科院分区：
文献类型：
--
作者：
CONSTANTINE, KL;DEMARCO, A;LLINAS, M
我们已经应用了计算程序，利用核磁共振数据来模拟铁铬铁的溶液构象，铁铬铁是一种已知x射线晶体结构的刚性微生物铁转运环六肽[D]。van der Helm et al.（1980）。化学。[j].生物工程学报，2016,42(2):422 - 431。在300、600和620 MHz下，通过一二维和二维1H-nmr研究了溶解在d6-二甲基亚砜（d6-DMSO）中的Al3+和Ga3+抗磁性类似物铝铬和胆铬。由质子Overhauser实验得到的质子间距离约束输入到距离几何算法[T.F.]哈维尔和K.乌斯里奇（1984）牛。数学。公牛。匹配。为了生成与实验数据一致的铁铬铁结构家族，随后通过抑制分子动力学/能量最小化进行优化[B.R.]布鲁克斯等人（1983）[j].化学学报，4,187-217。所得结构用相对能量和构象性质进行了表征。对包括14N-1H偶极相互作用在内的完整分子的广义块方程进行积分计算，结果表明x射线坐标很好地再现了实验核Overhauser效应的时间过程，并表明铁铬的结晶构象和溶液构象之间没有显著差异。一项类似的研究表明，在23度的d6-DMSO中至少存在两个构象。C.两者都不同于铁铬铁结构，并通过构象平均解释了观察到的酰胺NH和ch . α。多重谱线分裂。相互转换的肽骨架构象的发生产生序列nh - ch . α的数量增加。和NH-NH Overhauser连接，它反映了. ltbrac .r-6. rtbrac。偶极相互作用的依赖性。我们的结果支持这样一种观点，即在结构刚性肽的情况下，适度精确的距离约束定义了包含“真实”结构的构象子空间，并且能量考虑减小了该子空间的大小。然而，对于柔性肽，直接的方法可能会产生误导，因为核磁共振参数是在实质上不同的构象状态上平均的。
We have applied computatinal procedures that utilize nmr data to model the solution conformation of ferrichrome, a rigid microbial iron transport cyclohexapeptide of known x-ray crystallographic structure [D. van der Helm et al. (1980) J. Am. Chem. Soc. 102, 4224-4231]. The Al3+ and Ga3+ diamagnetic analogues, alumichrome and gallichrome, dissolved in d6-dimethylsulfoxide (d6-DMSO), were investigated via one- and two-dimensional 1H-nmr spectroscopy at 300, 600, and 620 MHz. Interproton distance constraints derived from proton Overhauser experiments were input to a distance geometry algorithm [T.F. Havel and K. Wuthrich (1984) Bull. Math. Bull. Match. Biol. 46, 673-691] in order to generate a family of ferrichrome structures consistent with the experimental data were subsequently optimized through restrained molecular dynamics/energy minimization [B.R. Brooks et al. (1983) J. Comp. Chem. 4, 187-217]. The resulting structures were characterized in terms of relative energies and conformational properties. Computations based on integration of the generalized Block equations for the complete molecule, which include the 14N-1H dipolar interaction, demonstrate that the x-ray coordinates reproduce the experimental nuclear Overhauser effect time courses very well, and indicate that there are no significant differences between the crystalline and solution conformations of ferrichrome. A similar study of the metal free peptide, deferriferrichrome, suggests that at least two conformers are present in d6-DMSO at 23.degree. C. Both are different from the ferrichrome structure and explain, through conformatinoal averaging, the observed amide NH and CH.alpha. multiplet splittings. The occurrence of interconverting peptide backbone conformations yields an increased number of sequential NH-CH.alpha. and NH-NH Overhauser connectivities, which reflects the .ltbbrac.r-6.rtbbrac. dependence of the dipolar interaction. Our results support the idea that, in the case of structurally rigid peptides, moderately accurate distance constraints define a conformational subspace encompassing the "true" structure, and that energy considerations reduce the size of this subspace. For flexible peptides, however, the straightforward approach can be misleading since the nmr parameters are averaged over substantially different conformatinal states.