Filgueira de Azevedo Walter, dos Santos Giovanni César, dos Santos Denis Marangoni, Olivieri Johnny Rizzieri, Canduri Fernanda, Silva Rafael Guimarães, Basso Luiz Augusto, Renard Gaby, da Fonseca Isabel Osório, Mendes Maria Anita, Palma Mário Sérgio, Santos Diógenes Santiago
Departamento de Física, UNESP, São José do Rio Preto, SP 15054-000, Brazil.
Biochem Biophys Res Commun. 2003 Oct 3;309(4):923-8.
Docking simulations have been used to assess protein complexes with some success. Small angle X-ray scattering (SAXS) is a well-established technique to investigate protein spatial configuration. This work describes the integration of geometric docking with SAXS to investigate the quaternary structure of recombinant human purine nucleoside phosphorylase (PNP). This enzyme catalyzes the reversible phosphorolysis of N-ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency due to mutations in the gene encoding for PNP causes gradual decrease in T-cell immunity. Inappropriate activation of T-cells has been implicated in several clinically relevant human conditions such as transplant rejection, rheumatoid arthritis, lupus, and T-cell lymphomas. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. The present analysis confirms the trimeric structure observed in the crystal. The potential application of the present procedure to other systems is discussed.
对接模拟已被用于评估蛋白质复合物，并取得了一定成功。小角X射线散射（SAXS）是一种成熟的研究蛋白质空间构型的技术。这项工作描述了将几何对接与SAXS相结合，以研究重组人嘌呤核苷磷酸化酶（PNP）的四级结构。该酶催化嘌呤核苷和脱氧核苷的N-核糖苷键的可逆磷酸解。由于编码PNP的基因突变导致的遗传缺陷会导致T细胞免疫力逐渐下降。T细胞的不适当激活与多种临床相关的人类疾病有关，如移植排斥、类风湿性关节炎、狼疮和T细胞淋巴瘤。因此，PNP是旨在调节T细胞免疫反应的抑制剂开发的靶点，并已进行了广泛的基于结构的药物设计。目前的分析证实了晶体中观察到的三聚体结构。讨论了本方法在其他系统中的潜在应用。
