Protocatechuate 3,4-dioxygenase
Protocatechuate dioxygenase breaks open the ring of catechol by adding molecular oxygen to the bond between two hydroxyl groups. It is important in the detoxification and breakdown of aromatic compounds by bacteria. It also has a role in the pathway of phenylalanine metabolism.
Reference Protein and Structure
- Sequences
-
P00436
(1.13.11.3)
P00437 (1.13.11.3)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Pseudomonas putida (Bacteria)
- PDB
-
3pca
- STRUCTURE OF PROTOCATECHUATE 3,4-DIOXYGENASE COMPLEXED WITH 3,4-DIHYDROXYBENZOATE
(2.2 Å)
- Catalytic CATH Domains
-
2.60.130.10
(see all for 3pca)
- Cofactors
- Water (1), Iron(3+) (1)
Enzyme Reaction (EC:1.13.11.3)
Enzyme Mechanism
Introduction
The catalytic iron ion directly chelates the two hydroxyl groups on the catechol aromatic ring. This process displaces the hydroxyl and tyrosine 447, which then act as bases in extracting protons from both the hydroxyl groups. Addition of molecular oxygen then takes place across the bond between the hydroxyls, The tyrosine 447 and water molecule then act as acids and donate protons back to the oxygen atoms leaving the product and a regenerated iron and ligands.
Catalytic Residues Roles
| UniProt | PDB* (3pca) | ||
| Arg158 | Arg457(157)M(B) | The negatively charged intermediates are stabilised by the positive charge on the Arg457. | electrostatic stabiliser |
| Tyr148 | Tyr447(147)M(B) | Forms part of the iron binding site in the ground state of the protein. It is displaced by the substrate and then acts as a general acid/base during the course of the reaction. | proton shuttle (general acid/base), metal ligand |
| Tyr109, His161, His163 | Tyr408(108)M(B), His460(160)M(B), His462(162)M(B) | Forms part of the iron binding site. | metal ligand |
Chemical Components
References
- Knoot CJ et al. (2015), Proc Natl Acad Sci U S A, 112, 388-393. Crystal structures of alkylperoxo and anhydride intermediates in an intradiol ring-cleaving dioxygenase. DOI:10.1073/pnas.1419118112. PMID:25548185.
- Vetting MW et al. (2000), Biochemistry, 39, 7943-7955. Structure ofAcinetobacterStrain ADP1 Protocatechuate 3,4-Dioxygenase at 2.2 Å Resolution: Implications for the Mechanism of an Intradiol Dioxygenase†. DOI:10.1021/bi000151e.
- Orville AM et al. (1997), Biochemistry, 36, 10052-10066. Crystal Structures of Substrate and Substrate Analog Complexes of Protocatechuate 3,4-Dioxygenase: Endogenous Fe3+Ligand Displacement in Response to Substrate Binding†,‡. DOI:10.1021/bi970469f. PMID:9254600.
- Orville AM et al. (1997), Biochemistry, 36, 10039-10051. Structures of Competitive Inhibitor Complexes of Protocatechuate 3,4-Dioxygenase: Multiple Exogenous Ligand Binding Orientations within the Active Site†,‡. DOI:10.1021/bi970468n. PMID:9254599.
- Que L Jr et al. (1996), Chem Rev, 96, 2607-2624. Dioxygen Activation by Enzymes with Mononuclear Non-Heme Iron Active Sites. DOI:10.1021/cr960039f. PMID:11848838.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| Tyr447(147)M(B) | proton shuttle (general acid/base) |
| Tyr408(108)M(B) | metal ligand |
| His460(160)M(B) | metal ligand |
| His462(162)M(B) | metal ligand |
| Arg457(157)M(B) | electrostatic stabiliser |
| Tyr447(147)M(B) | metal ligand |