T FOETUS IMPDH W/ NAD+

肌苷-5‘-单磷酸脱氢酶(IMPDH)催化NAD 依赖于将IMP氧化为黄嘌呤单磷酸(XMP)， 一磷酸鸟苷生物合成的承诺步骤。我们有 脱脂蛋白中胎毛虫IMPDH的晶体结构测定 2.3E分辨率下的形成和2.6E分辨率下的酶-XMP复合体 决议。而XMP在络合物中的电子密度 结构定义良好，NAD+结合位点和附近的环 含有催化型半胱氨酸的(Cys-319)是无序的。这 活动部位的紊乱表明高度的灵活性 可能是IMPDH催化功能所固有的，使这一区域成为 基于结构的缓蚀剂设计的困难目标。我们有 最近用NAD+共结晶了胎儿弓形虫IMPDH，并收集了 在我们的R轴IV上的3.5E分辨率的数据。我们希望获得数据以 2.5E在SSRL。NAD+可能有助于稳定这些地点， 促进了抑制剂的基于结构的设计。

Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the NAD dependent oxidation of IMP to xanthosine monophosphate (XMP), the committed step in guanosine monophosphate biosynthesis. We have determined the crystal structures of IMPDH from T. foetus in the apo form at 2.3 E resolution and the enzyme-XMP complex at 2.6 E resolution. While the electron density for XMP in the complex structure is well-defined, the NAD+ binding site and a nearby loop containing the catalytic cysteine (Cys-319) are disordered. This disorder at the active site suggests that a high degree of flexibility may be inherent to the catalytic function of IMPDH, making this area a difficult target for structure-based inhibitor design. We have recently co-crystallized T. foetus IMPDH with NAD+ and have collected data to 3.5 E resolution on our R-axis IV. We hope to obtain data to 2.5 E at SSRL. The NAD+ may help to stabilize these sites, facilitating the structure based design of inhibitors.