2C13

5-hydroxy-levulinic acid bound to Porphobilinogen synthase from Pseudomonas aeruginosa

Summary for 2C13

• Entry DOI: 10.2210/pdb2c13/pdb
• Related: 1B4K 1GZG 1W54 1W56 1W5M 1W5N 1W5O 1W5P 1W5Q 2C14 2C15 2C16 2C18 2C19
• Descriptor: DELTA-AMINOLEVULINIC ACID DEHYDRATASE, MAGNESIUM ION, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: enzyme mechanism, metalloenzyme, porphobilinogen synthase, cocrystallization, lyase, porphyrin biosynthesis
• Biological source: PSEUDOMONAS AERUGINOSA
• Total number of polymer chains: 2
• Total formula weight: 75184.33

Authors

Frere, F.,Nentwich, M.,Gacond, S.,Heinz, D.W.,Neier, R.,Frankenberg-Dinkel, N. (deposition date: 2005-09-11, release date: 2006-06-20, Last modification date: 2024-10-23)

Primary citation

Frere, F.,Nentwich, M.,Gacond, S.,Heinz, D.W.,Neier, R.,Frankenberg-Dinkel, N.
Probing the Active Site of Pseudomonas Aeruginosa Porphobilinogen Synthase Using Newly Developed Inhibitors.
Biochemistry, 45:8243-, 2006

PubMed Abstract: 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.

PubMed: 16819823
DOI: 10.1021/BI052611F

Experimental method

X-RAY DIFFRACTION (2.15 Å)