Potent anti-calmodulin activity of cyclotetradepsipeptides isolated from Isaria fumosorosea using a newly designed biosensor.
Seven cyclotetradepsipeptides, namely beauverolides C (1), F (2), I (3), Ja (4), L (5), M (6), and N (7), were isolated from the entomopathogenic fungus Isaria fumosorosea. The beauverolides were evaluated as potential calmodulin (CaM) inhibitors using the newly designed CaM biosensor hCaM M124C-AF350; these peptides displayed high affinity to the protein with dissociation constants (Kd) ranging from 0.078 μM to 3.44 μM. Beauverolide Ja, the only one containing a tryptophan residue in its structure, showed the highest affinity. The docking study predicted that beauverolides could bind to CaM in the same site of interaction as chlorpromazine, a well-known calmodulin ligand.
Abraham
A
Madariaga-Mazón
Martín
M
González-Andradeb
Conchita
C
Toriello
Hortensia
H
Navarro-Barranco
Rachel
R
Mata
D000818:Animals; D015374:Biosensing Techniques; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification*; D006430:Hemiptera / Q000382:microbiology; D010143:Paecilomyces / Q000737:chemistry*
D002147:Calmodulin; D047630:Depsipeptides; C013833:beauverolides