GLUCOSE-6-PHOSPHATE DEHYDROGENASE

点击翻译按钮获取中文摘要

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.