Studies of the mode of action of amiclenomycin.

ABSTRACT

Amiclenomycin (AM) was found to be a strong inhibitor of KAPA-DAPA aminotransferase of Brevibacterium divaricatum. This transamination was suggested to follow Ping Pong Bi Bi mechanism. Inhibition of this transamination by AM is of a noncompetitive type in a Lineweaver-Burk plot of initial velocity, but not in a Dixon plot. The activity of KAPA-DAPA aminotransferase drops abruptly after preincubation with AM, but its activity is restored by dialysis against 10 mM potassium phosphate buffer (pH 7.0). Inhibition by AM is decreased by an increase of KAPA in the reaction mixture, but not by an increase of S-adenosyl-L-methionine (SAM) or pyridoxal-5'-phosphate (PALP). These facts indicate that AM exerts its inhibitory action against KAPA-DAPA aminotransferase by binding to the enzyme, probably to the KAPA-DAPA binding site.