Inhibition of aminopeptidase M by alkyl D-cysteinates.
Ethyl D-cysteinate is a potent competitive inhibitor (Ki = 3.5 x 10(-7) M) of aminopeptidase M. D-cysteine and ethyl L-cysteinate inhibit more than two orders of magnitude less effectively. Inhibition studies on several n-alkyl esters of D-cysteine reveal an optimum at the n-butyl ester (Ki = 1.8 x 10(-7) M). The results are consistent with the hypothesis that the thiol group coordinates to Zn+2 at the active site and the alkyl group occupies the hydrophobic binding site for the side chain of the amino-terminal residue of substrates. Cytosolic leucine aminopeptidase is not significantly inhibited by ethyl D-cysteinate.
Bergin
J D
JD
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania 17837.
Clapp
C H
CH
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D018826:CD13 Antigens; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004952:Esters; D007536:Isomerism; D007700:Kinetics; D013329:Structure-Activity Relationship
D004952:Esters; D000626:Aminopeptidases; D018826:CD13 Antigens; D003545:Cysteine