Inhibition of Diamino Pelargonic Acid Aminotransferase, an Enzyme of the Biotin Biosynthetic Pathway, by Amiclenomycin: A Mechanistic Study
✍ Scribed by Stéphane Mann; Dominique Florentin; Denis Lesage; Thierry Drujon; Olivier Ploux; Andrée Marquet
- Book ID
- 102256219
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- German
- Weight
- 237 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
The mechanism of action of amiclenomycin (1a), a naturally occuring inhibitor of diaminopelargonic acid aminotransferase, has been established. The enzyme catalyzes the formation of an aromatic adduct between the inhibitor and pyridoxal‐5′‐phosphate. The structure of the adduct, determined by mass spectrometry, is in agreement with the reported X‐ray crystal structure. Kinetic parameters, characteristic of k~cat~ inhibitors, have been observed, with a K~I~ value of 2 μM and a k~inact~ value of 0.4 min^−1^. The irreversibility of the inactivation observed, in spite of the absence of covalent bond between the inhibitor and the protein, reveals the high affinity of the adduct for the active site. Two other cis‐1‐amino‐4‐substituted‐cyclohexa‐2,5‐dienes, 3a and 4a, were also found to efficiently inhibit the enzyme. The trans‐isomers were either much less potent (1b) or inactive (3b and 4b). The aminocyclohexadiene moiety, which is, apparently, responsible for the inhibition, could constitute an original pharmacophore for the design of new herbicides.