GLUCOSE-6-PHOSPHATE DEHYDROGENASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 葡萄糖-6-磷酸脱氢酶(G6PD)催化磷酸戊糖途径的第一步，生成核酸合成所需的戊糖。它将葡萄糖-6-磷酸(G6P)转化为6-磷酸葡萄糖酸，同时将NADP+还原为NADPH。NADPH是产生氧自由基的各种酶的重要还原剂，氧自由基可以刺激血管生成，从而增强肿瘤细胞对局部组织的侵袭，并上调血管炎症。临床研究表明，脱氢表雄酮(DHEA)是一种肾上腺类固醇，可以抑制G6PD，从而显著减轻炎症。 在这里，我们试图解决在DHEA存在下G6Pd的X射线结构。这为我们更好地了解DHEA对G6PD的抑制机制以及DHEA类似物作为潜在治疗药物的研究提供了详细的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The enzyme Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first step of the pentose phosphate pathway to produce pentoses for nucleic acid synthesis. It converts glucose-6-phosphate (G6P) to 6-phosphogluconate with the reduction of NADP+ to NADPH. NADPH serves as important reductant for various enzymes which generate oxygen-free radicals, which then can stimulate angiogenesis, thereby enhancing local tissue invasion by tumor cells, and upregulate vascular inflammation. Clinical studies show that dehydroepiandrosterone (DHEA), an adrenal steroid, can inhibit G6PD, thereby significantly lowering inflammation. Here we are trying to solve the X-ray structure of G6PD in the presence of DHEA. It can provide us detailed information to better understand the inhibitory mechanism of DHEA on G6PD and allow the study of DHEA-analogs as potential therapeutic drugs.