Sielecki A R, Hayakawa K, Fujinaga M, Murphy M E, Fraser M, Muir A K, Carilli C T, Lewicki J A, Baxter J D, James M N
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Science. 1989 Mar 10;243(4896):1346-51. doi: 10.1126/science.2493678.
The x-ray crystal structure of recombinant human renin has been determined. Molecular dynamics techniques that included crystallographic data as a restraint were used to improve an initial model based on porcine pepsinogen. The present agreement factor for data from 8.0 to 2.5 angstroms (A) is 0.236. Some of the surface loops are poorly determined, and these disordered regions border a 30 A wide solvent channel. Comparison of renin with other aspartyl proteinases shows that, although the structural cores and active sites are highly conserved, surface residues, some of which are critical for specificity, vary greatly (up to 10A). Knowledge of the actual structure, as opposed to the use of models based on related enzymes, should facilitate the design of renin inhibitors.
重组人肾素的X射线晶体结构已被确定。分子动力学技术（包括将晶体学数据作为约束条件）被用于改进基于猪胃蛋白酶原的初始模型。目前，8.0至2.5埃（Å）数据的拟合因子为0.236。一些表面环段的结构测定不佳，这些无序区域毗邻一个宽30 Å的溶剂通道。肾素与其他天冬氨酸蛋白酶的比较表明，尽管结构核心和活性位点高度保守，但表面残基（其中一些对特异性至关重要）差异很大（可达10 Å）。了解实际结构而非使用基于相关酶的模型，应有助于肾素抑制剂的设计。
