Acharya K R, Shapiro R, Riordan J F, Vallee B L
School of Biology and Biochemistry, University of Bath, United Kingdom.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2949-53. doi: 10.1073/pnas.92.7.2949.
The capacity of angiogenin (Ang) to induce blood vessel growth is critically dependent on its ribonucleolytic activity. Crystallography and mutagenesis of human Ang have previously shown that its pyrimidine binding site is obstructed by Gln-117, implying that a conformational change is a key part of the mechanism of Ang action. The 1.5-A-resolution crystal structure of bovine Ang, in which glutamic acid is substituted for Gln-117, now confirms that a blocked active site is characteristic of these proteins. Indeed, the inactive conformation of bovine Ang is stabilized by a more extensive set of interactions than is that of human Ang. The three-dimensional structure of the putative receptor binding site is also well conserved in the two proteins. The Arg-Gly-Asp segment of this site in bovine Ang, which is replaced by Arg-Glu-Asn in human Ang, does not have a conformation typical of an integrin recognition site.
血管生成素（Ang）诱导血管生长的能力关键取决于其核糖核酸酶活性。先前对人血管生成素的晶体学研究和诱变表明，其嘧啶结合位点被谷氨酰胺-117阻碍，这意味着构象变化是血管生成素作用机制的关键部分。现在，用谷氨酸取代谷氨酰胺-117的牛血管生成素的1.5埃分辨率晶体结构证实，活性位点受阻是这些蛋白质的特征。实际上，牛血管生成素的无活性构象通过比人血管生成素更广泛的一组相互作用得以稳定。这两种蛋白质中假定的受体结合位点的三维结构也高度保守。牛血管生成素中该位点的精氨酸-甘氨酸-天冬氨酸片段在人血管生成素中被精氨酸-谷氨酸-天冬酰胺取代，其构象并非典型的整合素识别位点构象。
