MS - 282a和MS - 282b，来自金牛座链霉菌ATCC 27470的钙调蛋白激活的肌球蛋白轻链激酶新抑制剂。

MS-282a and MS-282b, new inhibitors of calmodulin-activated myosin light chain kinase from Streptomyces tauricus ATCC 27470.

作者信息

Nakanishi S, Kita K, Uosaki Y, Yoshida M, Saitoh Y, Mihara A, Kawamoto I, Matsuda Y

机构信息

Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.

出版信息

J Antibiot (Tokyo). 1994 Aug;47(8):855-61. doi: 10.7164/antibiotics.47.855.

DOI:10.7164/antibiotics.47.855

PMID:7928670

Abstract

MS-282a and MS-282b were isolated from the culture broth of Streptomyces tauricus ATCC 27470 as inhibitors of smooth muscle myosin light chain kinase (MLCK). MS-282a and MS-282b inhibited the activity of chicken gizzard MLCK with IC50 values of 3.8 microM and 5.2 microM, respectively. Cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase and protein kinase C were not inhibited by 150 microM MS-282a at all. It is likely that MS-282a blocks MLCK activity by antagonizing calmodulin since 1) the compound inhibited calmodulin-dependent but not calmodulin-independent activity of MLCK; 2) the inhibition of MLCK was antagonized by increasing concentrations of calmodulin, and 3) the compound inhibited calmodulin-dependent cyclic nucleotide phosphodiesterase.

摘要

MS - 282a和MS - 282b是从牛链霉菌ATCC 27470的培养液中分离得到的，作为平滑肌肌球蛋白轻链激酶（MLCK）的抑制剂。MS - 282a和MS - 282b抑制鸡砂囊MLCK的活性，IC50值分别为3.8微摩尔和5.2微摩尔。150微摩尔的MS - 282a对环磷酸腺苷依赖性蛋白激酶、环磷酸鸟苷依赖性蛋白激酶和蛋白激酶C完全没有抑制作用。MS - 282a可能通过拮抗钙调蛋白来阻断MLCK的活性，因为：1）该化合物抑制MLCK的钙调蛋白依赖性活性，但不抑制其非钙调蛋白依赖性活性；2）增加钙调蛋白的浓度可拮抗对MLCK的抑制作用；3）该化合物抑制钙调蛋白依赖性环核苷酸磷酸二酯酶。