精氨酸的作用120人类前列腺素内过氧化物的H synthase-2与脂肪酸底物和抑制剂的交互。

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雷基CJ, Mulichak,无人RM,史密斯王

精氨酸的作用120人类前列腺素内过氧化物的H synthase-2与脂肪酸底物和抑制剂的交互。

生物化学杂志。1999年6月11日;274(24):17109 - 14所示。

PubMed ID

10358065 (在PubMed

]

文摘

参数- 120是疏水通道的口附近形成环氧酶活性部位的前列腺素内过氧化物H合成酶(PGHSs) 1和2。更换参数- 120绵羊的PGHS-1 PGHS-1谷氨酰胺增加明显公里的花生四烯酸的1000倍(Bhattacharyya d K。Lecomte, M。里克,c·J。,无人,r . M。史密斯,w . l .(1996)生物。271年化学,2179 - 2184)。这和其他证据表明,arg的胍基集团- 120与花生四烯酸的羧基形成离子键,这种相互作用是一个重要的贡献者PGHS-1花生四烯酸结合的整体实力。相比之下,我们在这里报告R120Q人类PGHS-2 (hPGHS-2)和本地hPGHS-2有非常相似的动力学性质,但R120L hPGHS-2催化花生四烯酸的氧化效率低下。我们的数据表明,arg的胍基集团- 120 hPGHS-2与花生四烯酸通过氢键相互作用而不是离子键,这种交互是更重要的花生四烯酸PGHS-2比PGHS-1有约束力。PGHS-1的Km值为花生四烯酸和2是一样的,和所有但一个核心残留的两个同功酶的活性区域是相同的。 Thus, the results of our studies of Arg-120 of PGHS-1 and -2 imply that interactions involved in the binding of arachidonate to PGHS-1 and -2 are quite different and that residues within the hydrophobic cyclooxygenase channel must contribute more significantly to arachidonate binding to PGHS-2 than to PGHS-1. As observed previously with R120Q PGHS-1, flurbiprofen was an ineffective inhibitor of R120Q hPGHS-2. PGHS-2-specific inhibitors including NS398, DuP-697, and SC58125 had IC50 values for the R120Q mutant that were up to 1,000-fold less than those observed for native hPGHS-2; thus, the positively charged guanido group of Arg-120 interferes with the binding of these compounds. NS398 did not cause time-dependent inhibition of R120Q hPGHS-2, whereas DuP-697 and SC58125 were time-dependent inhibitors. Thus, Arg-120 is important for the time-dependent inhibition of hPGHS-2 by NS398 but not by DuP-697 or SC58125.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Flurbiprofen	前列腺素合成酶1 G / H	蛋白质	人类	未知的	抑制剂	细节