Options
Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism
Auteur(s)
Frere, Frederic
Schubert, Wolf-Dieter
Stauffer, Frédéric
Frankenberg, Nicole
Jahn, Dieter
Heinz, Dirk
Date de parution
2002
In
Journal of Molecular Biology
Vol.
2
No
320
De la page
237
A la page
247
Mots-clés
Résumé
All natural tetrapyrroles, including hemes, chlorophylls and vitamin B-12, share porphobilinogen (PBG) as a common precursor. Porphobilinogen synthase (PBGS) synthesizes PBG through the asymmetric condensation of two molecules of aminolevulinic acid (ALA). Crystal structures of PBGS from various sources confirm the presence of two distinct binding sites for each ALA molecule, termed A and P. We have solved the structure of the active-site variant D139N of the Mg2+-dependent PBGS from Pseudomonas aeruginosa in complex with the inhibitor 5-fluorolevulinic acid at high resolution. Uniquely, full occupancy of both substrate binding sites each by a single substrate-like molecule was observed. Both inhibitor molecules are covalently bound to two conserved, active-site lysine residues, Lys205 and Lys260, through Schiff bases. The active site now also contains a monovalent cation that may critically enhance enzymatic activity. Based on these structural data, we postulate a catalytic mechanism for P. aeruginosa PBGS initiated by a C-C bond formation between A and P-side ALA, followed by the formation of the intersubstrate Schiff base yielding the product PBG. (C) 2002 Elsevier Science Ltd. All rights reserved.
Identifiants
Type de publication
journal article
