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Probing the Active Site of Pseudomonas aeruginosa Porphobilinogen Synthase Using Newly Developed Inhibitors

Auteur(s)
Frere, Frederic
Nentwich, Merle
Gacond, Sabine
Heinz, Dirk W.
Frankenberg-Dinkel, Nicole
Date de parution
2006
In
Biochemistry
Vol.
27
No
45
De la page
8243
A la page
8253
Mots-clés
Résumé
Porphobilinogen synthase catalyzes the first committed step of the tetrapyrrole biosynthesis pathway. In an aldol-like condensation, two mols. of 5-aminolevulinic acid (ALA) form the first pyrrole, porphobilinogen. Newly synthesized analogs of a reaction intermediate of porphobilinogen synthase have been employed in studying the active site and the catalytic mechanism of this early enzyme of tetrapyrrole biosynthesis. This study combines structural and kinetic evaluation of the inhibition potency of these inhibitors. In addn., one of the detd. protein structures provides for the first time structural evidence of a magnesium ion in the active site. From these results, we can corroborate an earlier postulated enzymic mechanism that starts with formation of a C-C bond, linking C3 of the A-side ALA to C4 of the P-side ALA through an aldole addn. The obtained data are discussed with respect to the current literature. [on SciFinder(R)]
Identifiants
https://libra.unine.ch/handle/123456789/21499
Type de publication
journal article