Options
Probing the Active Site of <i>Pseudomonas aeruginosa</i> Porphobilinogen Synthase Using Newly Developed Inhibitors
Auteur(s)
Frère, Frederic
Nentwich, Merle
Gacond, Sabine
Heinz, Dirk W.
Frankenberg-Dinkel, Nicole
Date de parution
2006
In
Biochemistry, American Chemical Society (ACS), 2006/45/27/8243–8253
Résumé
Porphobilinogen synthase catalyzes the first committed step of the tetrapyrrole biosynthesis pathway. In an aldol-like condensation, two molecules of 5-aminolevulinic acid (ALA) form the first pyrrole, porphobilinogen. Newly synthesized analogues 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 addition, one of the determined 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 enzymatic 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 addition. The obtained data are discussed with respect to the current literature.
Identifiants
Type de publication
journal article
Dossier(s) à télécharger
