人核糖核苷酸还原酶。ATP类似物对其的激活与抑制作用。

Human ribonucleotide reductase. Activation and inhibition by analogs of ATP.

作者信息

Harrington J A, Spector T

机构信息

Burroughs Wellcome Co., Wellcome Research Laboratories, Research Triangle Park, NC 27709.

出版信息

Biochem Pharmacol. 1991 Jul 25;42(4):759-63. doi: 10.1016/0006-2952(91)90033-2.

DOI:10.1016/0006-2952(91)90033-2

PMID:1867633

Abstract

Sixteen ATP analogs were studied as activators of CDP reduction catalyzed by human ribonucleotide reductase. Activation constants were determined. Three analogs, 3-deazaATP, 5'-adenylimidodiphosphate, and 3'-dATP, activated approximately as efficiently as ATP. Four analogs were partial activators. These seven activators were also accessory activators of GDP reduction. Furthermore, two other analogs, adenosine-5'-O-(1-thiotriphosphate) and 8-bromoATP, selectively stimulated GDP reduction. Ten analogs, at equal molar concentrations with ATP, inhibited ATP-dependent activation of CDP reduction and/or accessory activation of GDP reduction by greater than 45%. No analog inhibited as potently as 2'-dATP, which had an IC50 of 30-50 microM versus the stimulation of CDP and GDP reduction by 2.0 mM ATP.

摘要

研究了16种ATP类似物作为人核糖核苷酸还原酶催化的CDP还原激活剂的情况。测定了激活常数。三种类似物，即3-脱氮ATP、5'-腺苷亚氨二磷酸和3'-dATP，激活效率与ATP大致相同。四种类似物是部分激活剂。这七种激活剂也是GDP还原的辅助激活剂。此外，另外两种类似物，腺苷-5'-O-(1-硫代三磷酸)和8-溴ATP，选择性地刺激GDP还原。十种类似物在与ATP等摩尔浓度下，抑制CDP还原的ATP依赖性激活和/或GDP还原的辅助激活超过45%。没有一种类似物的抑制作用像2'-dATP那样强，2'-dATP对2.0 mM ATP刺激CDP和GDP还原的IC50为30-50 microM。