MIF ENZYMATIC INHIBITION

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。 巨噬细胞迁移抑制因子(MIF)是一种促炎细胞因子，可以抵消糖皮质激素的抗炎活性(Calandra和Bucala J.炎症47，PG。39,1995)。过度的MIF活性与许多疾病有关，包括败血症休克(Bernhgen等人)。自然，365分，PG。756,1993)，关节炎Mikulowska等人。《免疫学》158页。5514,1997)和癌症(Ren等人安。外科手术242页。55,2005)。MIF也被发现能促进大鼠的胰岛素分泌(Waeber等人)。PNAS 94，PG.4782,1997)。MIF不仅是一种细胞因子，而且还具有催化活性。尽管它的所有已知催化活性都涉及非生理底物，但抑制催化活性部位会抑制其促炎功能(Lubetsky等人)。J.Biol.化学。277页，第24976页，2002年)。我们希望在这个催化位置获得与MIF结合的化合物的高分辨结构。

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. Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine that counteracts the anti-inflammatory activities of glucocorticoids (Calandra and Bucala J. Inflammation 47, pg. 39, 1995). Excessive MIF activity has been implicated in a number of diseases, including septic shock (Bernhagen et al. Nature 365, pg. 756, 1993), arthritis Mikulowska et al. J. Immunology 158, pg. 5514, 1997) and cancer (Ren et al. Ann. Surg. 242, pg. 55,2005). MIF has also been found to enhance insulin secretion in rats (Waeber et al. PNAS 94, pg. 4782, 1997). Not only is MIF a cytokine, but it also has catalytic activity. Although all of its known catalytic activities involve non-physiological substrates, inhibiting the catalytic active-site inhibits its pro-inflammatory function (Lubetsky et al. J. Biol. Chem. 277, pg.24976, 2002). We hope to obtain high-resolution structures of compounds bound to MIF in this catalytic site.