Small-molecule inhibitor: amastatin

Name

History: Amastatin, a product of actinomycetes, was described as an inhibitor of aminopeptidase A by Aoyagi et al. (1978).
Peptidases inhibited: Amastatin inhibits <#Aeromonas aminopeptidase#M28.002#>, aminopeptidase N, aminopeptidase A and leucyl aminopeptidase (Tobe et al., 1980; Wilkes et al., 1985). Aminopeptidase B is not inhibited (Nagata et al., 1991).
Mechanism: Inhibition is reversible and competitive, but also slow, so that measurements of K_i are not simple. K_i values reported have been approximately: 3x10^-10 M (Aeromonas aminopeptidase: Wilkes et al., 1985), 4x10^-8 M (aminopeptidase N: Wilkes et al., 1985), 6x10^-8 M (leucyl aminopeptidase: Wilkes et al., 1985) and 2x10^-7 M (aminopeptidase A: Tobe et al., 1980; Sakura et al., 1983). The two N-terminal residues of amastatin apparently bind in the S1 and S1" sites of leucyl aminopeptidase, spanning the catalytic site, and the likely mechanism of slow binding has been discussed (Kim & Lipscomb, 1993).

CID at PubChem: 439518
ChEBI: 2624
Structure
Chemical/biochemical name: [(2S, 3R)]-3-amino-2-hydroxy-5-methylhexanoyl]-Val-Val-Asp
Formula weight: 475