Aromatic-ring-hydroxylating dioxygenases

Aromatic-ring-hydroxylating dioxygenases (ARHD) incorporate two atoms of dioxygen (O₂) into their substrates in the dihydroxylation reaction. The product is (substituted) "cis"-1,2-dihydroxycyclohexadiene, which is subsequently converted to (substituted) benzene glycol by a "cis"-diol dehydrogenase.

A large family of multicomponent mononuclear (non-heme) iron oxygenases has been identified. Components of bacterial aromatic-ring dioxygenases constitute two different functional classes: hydroxylase components and electron transfer components. Hydroxylase components are either (αβ)_"n" or (α)_"n" oligomers. Two prosthetic groups, a Rieske-type [Fe₂S₂] center and a mononuclear iron, are associated with the α-subunit in the (αβ)_"n"-type enzymes. Electron transfer components are composed of flavoprotein (NADH:ferredoxin oxidoreductase) and Rieske-type [Fe₂S₂] ferredoxin. In benzoate and toluate 1,2-dioxygenase systems, a single protein containing reductase and Rieske-type ferredoxin domains transfers the electrons from NADH to the hydroxylase component. In the phthalate 4,5-dioxygenase system, phthalate dioxygenase reductase (PDR) has the same function. PDR is a single protein comprising FMN-binding reductase and plant-type ferredoxin domains. Thus, the electron transfer in ARHD systems can be summarised as:

Biochemical classification

EC number|1.14.12.3 benzene 1,2-dioxygenase: benzene + NADH + H⁺ + O₂ = "cis"-cyclohexa-3,5-diene-1,2-diol + NAD⁺

EC number|1.14.12.7 phthalate 4,5-dioxygenase: phthalate + NADH + H⁺ + O₂ = "cis"-4,5-dihydroxycyclohexa-1(6),2-diene-1,2-dicarboxylate + NAD⁺

EC number|1.14.12.8 4-sulfobenzoate 3,4-dioxygenase: 4-sulfobenzoate + NADH + H⁺ + O₂ = 3,4-dihydroxybenzoate + sulfite + NAD⁺

EC number|1.14.12.9 4-chlorophenylacetate 3,4-dioxygenase: 4-chlorophenylacetate + NADH + H⁺ + O₂ = 3,4-dihydroxyphenylacetate + chloride + NAD⁺

EC number|1.14.12.10 benzoate 1,2-dioxygenase: benzoate + NADH + H⁺ + O₂ = 1,2-dihydroxycyclohexa-3,5-diene-1-carboxylate + NAD⁺

EC number|1.14.12.11 toluene dioxygenase: toluene + NADH + H⁺ + O₂ = (1"S",2"R")-3-methylcyclohexa-3,5-diene-1,2-diol + NAD⁺

EC number|1.14.12.12 naphthalene 1,2-dioxygenase: naphthalene + NADH + H⁺ + O₂ = (1"R",2"S")-1,2-dihydronaphthalene-1,2-diol + NAD⁺

EC number|1.14.12.15 terephthalate 1,2-dioxygenase: terephthalate + NADH + H⁺ + O₂ = (1"R",6"S")-dihydroxycyclohexa-2,4-diene-1,4-dicarboxylate + NAD⁺

EC number|1.14.12.18 biphenyl 2,3-dioxygenase: biphenyl + NADH + H⁺ + O₂ = (1"S",2"R")-3-phenylcyclohexa-3,5-diene-1,2-diol + NAD⁺

tructure

The crystal structure of the hydroxylase component of naphthalene 1,2-dioxygenase from "Pseudomonas" has been determined. The protein is an (αβ)₃ hexamer. The β-subunit belongs to theα+β class. It has no prosthetic groups and its role in catalysis is unknown. The α-subunit can be divided into two domains: a Rieske domain that contains the [Fe₂S₂] center and the catalytic domain that contains the active site mononuclear iron. The Rieske domain (residues 38-158) consists of four β-sheets. The overall fold is very similar to that of the soluble fragment of the Rieske protein from bovine heart mitochondrial cytochrome "bc"₁ complex. In the [Fe₂S₂] center, Fe1 is coordinated by two cysteine residues (Cys-81 and Cys-101) while Fe2 is coordinated by N^δ atoms of two histidine residues (His-83 and His-104). The catalytic domain belongs to the α+β class and is dominated by a nine-stranded antiparallel β-sheet. The iron of the active site is located at the bottom of a narrow channel, approximately 15 Å from the protein surface. The mononuclear iron is coordinated by His-208, His-213, Asp-362 (bidentate) and a water molecule. The geometry can be described as a distorted octahedral with one ligand missing. The structure of the hexamer suggests cooperativity between adjacent α-subunits, where electrons from the [Fe₂S₂] center in one α-subunit (A) are transferred to the mononuclear iron in the adjacent α-subunit (B) through Asp_B-205, which is hydrogen-bonded to His_A-104 of the Rieske center and His_B-208 of the active site.

References

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External links

* - structure of napthalene 1,2-dioxygenase from "Pseudomonas putida"
* - structure of biphenyl 2,3-dioxygenase from "Rhodococcus" sp. strain RHA1
* - InterPro entry for Bacterial ring hydroxylating dioxygenase, alpha subunit