MS-347a, a new inhibitor of myosin light chain kinase from Aspergillus sp. KY52178.
MS-347a was isolated from the culture broths of Aspergillus sp. KY52178 as an inhibitor of smooth muscle myosin light chain kinase (MLCK). MS-347a inhibited the activity of chicken gizzard MLCK with an IC50 value of 9.2 microM. The inhibition was dependent on time of preincubation of MS-347a with the enzyme, suggesting irreversible inhibition. It is likely that the inhibitor binds to the catalytic domain of MLCK, since the compound inhibited not only calmodulin-dependent but also calmodulin-independent activity of MLCK. Calmodulin-dependent cyclic nucleotide phosphodiesterase, cAMP-dependent protein kinase and cGMP-dependent protein kinase were not inhibited by 150 microM MS-347a at all, although the compound inhibited protein kinase C with an IC50 value of 16 microM. MS-347b, a minor component was also isolated from the same culture broths. This minor component at 150 microM did not inhibit the activity of MLCK.
Nakanishi
S
S
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Ando
K
K
Kawamoto
I
I
Matsuda
Y
Y
D001230:Aspergillus / Q000737:chemistry / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002867:Chromones / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D005285:Fermentation; D007700:Kinetics; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*
D002867:Chromones; D004852:Epoxy Compounds; C085608:MS 347a; D009219:Myosin-Light-Chain Kinase