PURINE NUCLEOSIDE PHOSPHORYLASE: NOVEL CHEMOTHER FOR LYMPHOMA & GRAFT REJECTION

嘌呤核苷磷酸化酶（PNP）催化磷酸化 嘌呤核苷产生游离嘌呤，1-核糖磷酸 人类的一种遗传缺陷导致PNP缺乏， T细胞完全丧失但没有其他影响 因此，PNP是一种 一个很好的目标，用于治疗一些T细胞特异性 病理学包括T细胞淋巴瘤和移植排斥。 我们有 最近收集的数据显示，小牛之间的复合体优于2.0E 脾PNP和20 pM过渡态抑制剂。 细化 正在进行中，目前揭示了几个使用的战略， 酶来稳定过渡态，其包括 构象重排 这个结构代表了 最高亲和力的酶-配体复合物解决了日期，并将形成 为今后的抑制剂开发和机理研究奠定了基础。

Purine nuceloside phosphorylase (PNP) catalyzes the phosphorolysis of purine nucleosides to yield free purines and ?-1-ribose phosphate. A genetic defect in humans that results in the lack of PNP, results in a complete loss of T-cells, but no other effects. Thus PNP is an excellent target for the therapy of a number of T-cell specific pathologies including T-cell lymphomas and graft rejection. We have recently collected data to better than 2.0E on a complex between calf spleen PNP and a 20 pM transition state-inhibitor. Refinement is underway and currently reveals several of the strategies used by this enzyme to stabilize the transition state, which includes a conformational rearrangement. This structure represents one of the highest affinity enzyme-ligand complexes solved to date and will form the basis for future inhibitor development and mechanistic studies.