Szyperski T, Fernández C, Mumenthaler C, Wüthrich K
Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule-Hönggerberg, CH-8093 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2262-6. doi: 10.1073/pnas.95.5.2262.
The human glioma pathogenesis-related protein (GliPR) is highly expressed in the brain tumor glioblastoma multiforme and exhibits 35% amino acid sequence identity with the tomato pathogenesis-related (PR) protein P14a, which has an important role for the plant defense system. A molecular model of GliPR was computed with the distance geometry program DIANA on the basis of a P14a-GliPR sequence alignment and a set of 1,200 experimental NMR conformational constraints collected with P14a. The GliPR structure is represented by a group of 20 conformers with small residual DIANA target function values, low AMBER-energies after restrained energy-minimization with the program OPAL, and an average rms deviation relative to the mean of 1.6 A for the backbone heavy atoms. Comparison of the GliPR model with the P14a structure lead to the identification of a common partially solvent-exposed spatial cluster of four amino acid residues, His-69, Glu-88, Glu-110, and His-127 in the GliPR numeration. This cluster is conserved in all known plant PR proteins of class 1, indicating a common putative active site for GliPR and PR-1 proteins and thus a functional link between the human immune system and a plant defense system.
人类胶质瘤发病机制相关蛋白（GliPR）在脑肿瘤多形性胶质母细胞瘤中高度表达，与番茄病程相关蛋白P14a具有35%的氨基酸序列同一性，而P14a对植物防御系统具有重要作用。基于P14a - GliPR序列比对以及用P14a收集的一组1200个实验性核磁共振构象约束条件，使用距离几何程序DIANA计算了GliPR的分子模型。GliPR结构由一组20个构象体表示，这些构象体具有较小的剩余DIANA目标函数值，在用OPAL程序进行受限能量最小化后具有较低的AMBER能量，并且相对于主链重原子平均值的平均均方根偏差为1.6 Å。将GliPR模型与P14a结构进行比较，在GliPR编号中鉴定出一个由四个氨基酸残基His - 69、Glu - 88、Glu - 110和His - 127组成的共同的部分暴露于溶剂的空间簇。该簇在所有已知的1类植物PR蛋白中都保守，这表明GliPR和PR - 1蛋白存在共同的假定活性位点，从而表明人类免疫系统与植物防御系统之间存在功能联系。
