MS-347a, A new inhibitor of myosin light chain kinase from aspergillus sp. ky52178

Abstract

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 9.2μM. 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 phospho diesterase, cAMP-dependent protein kinase and cGMP-dependent protein kinase were not inhibited by 150μm MS-347a at all, although the compound inhibited protein kinase C with an IC50 value of 16μm. MS-347b, a minor component was also isolated from the same culture broths. This minor component at 150 μm did not inhibit the activity of MLCK. © 1993, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.