MS-282a and MS-282b, new inhibitors of calmodulin-activated myosin light chain kinase from Streptomyces tauricus ATCC 27470.
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.
Nakanishi
S
S
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Kita
K
K
Uosaki
Y
Y
Yoshida
M
M
Saitoh
Y
Y
Mihara
A
A
Kawamoto
I
I
Matsuda
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002645:Chickens; D005285:Fermentation; D005663:Furans / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*
D005663:Furans; C089603:MS 282a; C089604:MS 282b; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase