Crystal structure of the hypoxanthine-guanine-xanthine phosphoribosyltransferase from the protozoan parasite Tritrichomonas foetus.
Crystal structure of the hypoxanthine-guanine-xanthine phosphoribosyltransferase from the protozoan parasite Tritrichomonas foetus.
复制标题
来自原生动物寄生虫胎儿三滴虫的次黄嘌呤-鸟嘌呤-黄嘌呤磷酸核糖基转移酶的晶体结构。
DOI：
10.1021/bi953072p
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Fletterick,RJ
中科院分区：
文献类型：
--
作者：
Somoza,JR;Chin,MS;Focia,PJ;Wang,CC;Fletterick,RJ
来自三毛单胞菌的次黄嘌呤-鸟嘌呤-黄嘌呤磷酸核糖基转移酶（HGXPRTase）的晶体结构已根据X射线数据确定并细化至1.9 Å分辨率。T.胎儿HGXPRTase结晶为不对称二聚体，GMP仅与形成不对称单元的两个分子之一结合。HGXPRTase的每个分子由两个由短“铰链”区连接的叶形成，GMP结合在两个叶之间的空腔中。在不对称单元中的两个分子的比较表明，铰链区是灵活的，并且配体结合影响两个裂片的相对位置。GMP的结合使两个叶更靠近在一起，使一个叶相对于另一个叶旋转约5°。胎儿似乎依赖于HGXPRTase来提供GMP，使这种酶成为抗寄生虫药物设计的靶点。胎毛癣菌HGXPRT酶和人HGPRT酶的结构比较表明，虽然这些酶保留了相似的多肽折叠，但这两种同源物的活性位点之间存在实质性差异。这些差异表明，有可能找到选择性抑制寄生虫酶的化合物。
The crystal structure of the hypoxanthine−guanine−xanthine phosphoribosyltransferase (HGXPRTase) fromTritrichomonasfoetushas been determined and refined against X-ray data to 1.9 Å resolution.T. foetusHGXPRTase crystallizes as an asymmetric dimer, with GMP bound to only one of the two molecules that form the asymmetric unit. Each molecule of HGXPRTase is formed by two lobes joined by a short “hinge” region, and the GMP binds in a cavity between the two lobes. A comparison of the two molecules in the asymmetric unit shows that the hinge region is flexible and that ligand binding affects the relative positions of the two lobes. The binding of GMP brings the two lobes closer together, rotating one lobe by about 5° relative to the other.T. foetusappears to depend on HGXPRTase for its supply of GMP, making this enzyme a target for antiparasite drug design. A comparison of the structures ofT.foetusHGXPRTase and human HGPRTase reveals that, while these enzymes retain a similar polypeptide fold, there are substantial differences between the active sites of these two homologs. These differences suggest that it will be possible to find compounds that selectively inhibit the parasite enzyme.