Conformationally restricted creatine analogues and substrate specificity of rabbit muscle creatine kinase.
Conformationally restricted creatine analogues and substrate specificity of rabbit muscle creatine kinase.
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兔肌肉肌酸激酶的构象限制肌酸类似物和底物特异性。
DOI：
10.1021/bi00555a011
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发表时间：
1980
期刊：
影响因子：
2.9
通讯作者：
Reed,GH
中科院分区：
文献类型：
--
作者：
Dietrich,RF;Miller,RB;Kenyon,GL;Leyh,TS;Reed,GH
Robert F. Dietrich，1 Robert B.米勒，乔治L. Kenyon，** 托马斯S. Leyh和乔治H. Reed摘要：合成了几种构象受限的肌酸类似物，并将其作为兔肌肌酸激酶（EC 2.7）的潜在底物或抑制剂进行了研究。3.2）。当一个不对称的中心包括在肌酸类似物中的位置a的羧基，酶有一个明显的R对映体的偏好。因此，尽管（J？）-. N-脒基氮杂环丁烷-2-羧酸（7）已显示为肌酸激酶的良好底物（Ks= 72 mM，Km=39 mM，且Fmax= 29%，相对于肌酸的底物），相应的S '对映异构体6仅显示几乎不可检测的反应性（Fmax（rel）~ 1%）。当相应的开环类似物N-甲基-A ′-脒基丙氨酸作为底物进行检测时，肌酸激酶再次显示出对R对映体9的强烈偏好[Ks= 94 mM，Km= 82 mM，Fmax（rel）10%]。R对映体的反应性比S对映体高约7倍
Robert F. Dietrich, 1 Robert B. Miller, George L. Kenyon,** Thomas S. Leyh, and George H. Reed abstract: Several conformationally restricted analogues of creatine havebeen both synthesized and examined as potential substrates or inhibitors of rabbit muscle creatine kinase (EC 2.7. 3.2). When an asymmetric center was included in a creatine analogue in the position a to the carboxyl group, the enzyme had a pronounced preference for the R enantiomer. Thus, whereas (J?)-./V-amidinoazetidine-2-carboxylic acid (7) has been shown to be a good substrate (Ks= 72 mM, Km=39 mM, and Fmax= 29% relative to that of creatine) for creatine kinase, the corresponding S’enantiomer 6 showed only barely detectable reactivity (Fmax (rel)«1%). When the corresponding ring-opened analogue, TV-methyl-A'-amidinoalanine, was examined as a substrate, creatine kinase again showed a strong preference for the R enantiomer 9 [Ks= 94 mM, Km= 82 mM, Fmax (rel) 10%]. The R enantiomer was approximately 7 times more reactive than its S enantiomer