Refinement of the solution structure of the heparin-binding domain of vascular endothelial growth factor using residual dipolar couplings
Refinement of the solution structure of the heparin-binding domain of vascular endothelial growth factor using residual dipolar couplings
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DOI：
10.1023/a:1015346504499
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发表时间：
2002-05-01
影响因子：
2.7
通讯作者：
Fairbrother, WJ
中科院分区：
文献类型：
--
作者：
Stauffer, ME;Skelton, NJ;Fairbrother, WJ
先前对血管内皮生长因子(VEGF165)的肝素结合域的核磁共振结构研究揭示了一个新的折叠结构，它由两个亚域组成，每个亚域包含两个二硫键和一个短的双链反平行的β-折叠。核磁共振数据不能很好地确定两个亚域的相互取向。异核弛豫数据表明，这种紊乱是由于界面尺寸有限而相对缺乏实验约束造成的，而不是固有的高频灵活性。使用H-1(N)-N-15残余偶极耦合约束对结构进行细化，显著提高了相对亚区取向的清晰度。
Previous NMR structural studies of the heparin-binding domain of vascular endothelial growth factor (VEGF(165)) revealed a novel fold comprising two subdomains, each containing two disulfide bridges and a short two-stranded antiparallel beta-sheet. The mutual orientation of the two subdomains was poorly defined by the NMR data. Heteronuclear relaxation data suggested that this disorder resulted from a relative lack of experimental restraints due to the limited size of the interface, rather than inherent high-frequency flexibility. Refinement of the structure using H-1(N)-N-15 residual dipolar coupling restraints results in significantly improved definition of the relative subdomain orientations.