1gzg

From Proteopedia

Revision as of 13:38, 18 December 2007

COMPLEX OF A MG2-DEPENDENT PORPHOBILINOGEN SYNTHASE FROM PSEUDOMONAS AERUGINOSA (MUTANT D139N) WITH 5-FLUOROLEVULINIC ACID

Overview

All natural tetrapyrroles, including hemes, chlorophylls and vitamin B12, 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.

About this Structure

1GZG is a Single protein structure of sequence from Pseudomonas aeruginosa with MG, NA, SO4, K and LAF as ligands. Active as Porphobilinogen synthase, with EC number 4.2.1.24 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism., Frere F, Schubert WD, Stauffer F, Frankenberg N, Neier R, Jahn D, Heinz DW, J Mol Biol. 2002 Jul 5;320(2):237-47. PMID:12079382

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