| Root |
Created: 6 October 1997
| Centre | Prosthetic group | Formal oxidation states | |
|---|---|---|---|
| Fe2S2I |
  Cys)4 |
||
| Fe2S2II | |||
| Moco |  |
||
 (active) |
 (inactive) |
||
| FAD |
 |
FAD· (semiquinone); FADH2 |
|
Enzymes of the xanthine oxidase family contain a molybdenum cofactor (Moco) and
[Fe2S2] clusters and catalyse the oxidative hydroxylation
of a range of aromatic heterocyclic compounds (X) and aldehydes (RCHO) in
reactions that involve the cleavage of a C-H bond
[1, 2].
Note that product tautomerisation
(X-OH 
X=O) in reactions of hydroxylation
of heterocyclic substrates (1, 2) usually results in the keto rather
than enol form of the product [3].
Desulfovibrio gigas aldehyde oxidoreductase and the eukaryotic
xanthine oxidase, xanthine dehydrogenase and aldehyde oxidase are
Xanthine oxidase
XH + H2O + O2
X=O + H2O2
(1)
Xanthine dehydrogenase
XH + H2O + NAD+
X=O + NADH
(2)
Aldehyde oxidase
RCHO + H2O + O2
RCOOH + H2O2
(3)
2 homodimers.
Each monomer is organised into several domains. The first two domains
each coordinate an [Fe2S2] cluster; they are followed by
a flavin domain (absent in D. gigas aldehyde oxidoreductase) and
finally the two domains which bind one molecule of Moco.
The remaining enzymes of this family have their redox centres in separate
subunits. Enzymes lacking a flavin centre are generally organised as
(ß)n
(n = 1, 2) with two [Fe2S2] clusters in the
subunit and Moco in the
ß subunit; enzymes with a flavin centre are generally organised as
(ß)n
(n = 1, 2) with two [Fe2S2] clusters in the
subunit, the flavin in the
ß subunit and Moco in the
subunit [2, 3 and
references therein].
In eukaryotic enzymes the pterin cofactor is molybdopterin, while in
prokaryotic enzymes it can be found as the dinucleotide of guanine, cytosine,
adenine or hypoxanthine [3].
The 3D structure of Desulfovibrio gigas aldehyde oxidoreductase
(Mop) has been determined
[4, 5]
(see Figure 1ALO). Mop is a homodimer with each
subunit containing a molybdenum coordinated by a molybdopterin cytosine
dinucleotide and two [Fe2S2] clusters. Each monomer is
folded into four domains, of which the first two bind the iron-sulphur
clusters (Fe2S2I and
Fe2S2II) and the others bind Moco
(MocoI and MocoII). The Fe2S2I domain
(residues 1-74) has a fold similar to that of
planttype ferredoxins while the
Fe2S2II domain (residues 74-157) folds into a
fourhelix bundle.
MocoI (residues 196-581) is a mainlyß domain which provides
much of the binding interactions to the molybdopterin. MocoII (residues
581-907) is an /ß domain which
forms the remaining interactions to the molybdopterin and all of the
interactions to the cytosine nucleotide. The Moco is buried within the
MocoI and MocoII domains and is accessible through a
15Ådeep tunnel.
The molybdenum is pentacoordinated with an approximately square pyramidal
coordination geometry. The two dithiolene sulphur atoms of the
molybdopterin and two oxygen ligands form the equatorial plane, whereas the
apical site is occupied either by a sulphido group in the functional sulpho
form of the enzyme or by an oxygen ligand in the inactive desulpho form
[1, 5].
On the basis of the kinetic studies on xanthine oxidase [6] and the 3D structure of Mop, electron transfer within xanthine oxidase can be summarised [3] as
| Xanthine oxidase | FAD |
|
Fe2S2I |
|
Fe2S2II |
|
Moco |
|
Substrate | (1.1) |
| ENZYME | LIGAND | BRENDA | Official name | Alternative name(s) |
|---|---|---|---|---|
| 1.1.1.204 | 1.1.1.204 | 1.1.1.204 | Xanthine dehydrogenase | Xanthine-NAD+ oxidoreductase |
| 1.1.3.22 | 1.1.3.22 | 1.1.3.22 | Xanthine oxidase | Hypoxanthine oxidase |
| 1.2.3.1 | 1.2.3.1 | 1.2.3.1 | Aldehyde oxidase | Quinoline oxidase |
| 1.2.3.10 | 1.2.3.10 | 1.2.3.10 | Carbon monoxide oxidase | CO dehydrogenase; CO oxidoreductase |
| 1.3.99.16 | 1.3.99.16 | Isoquinoline 1oxidoreductase | ||
| 1.3.99.17 | 1.3.99.17 | Quinoline 2oxidoreductase | ||
| 1.3.99.19 | 1.3.99.19 | Quinoline4carboxylic acid 2oxidoreductase | Quinaldine4oxidoreductase; quinaldic acid 4oxidoreductase | |
| 1.5.1.13 | 1.5.1.13 | 1.5.1.13 | Nicotinate dehydrogenase | Nicotinic acid hydroxylase |
| 1.5.99.4 | 1.5.99.4 | 1.5.99.4 | Nicotine dehydrogenase | Nicotine oxidase |
| PRINTS ID | PRINTS AC | PROSITE/BLOCKS ID | PROSITE AC | BLOCKS AC |
|---|---|---|---|---|
| 2FE2SFRDOXIN | PR00159 | 2FE2S_FERREDOXIN | PS00197 | BL00197 |
| MOLYBDOPTERIN_EUK | PS00559 | BL00559 |
| Protein Family | Protein Homology Domain | Pfam | LPFC 3D alignment |
|---|---|---|---|
|
03772;
xanthine dehydrogenase
03857; Desulfovibrio gigas aldehyde oxidase |
00254; ferredoxin [2Fe-2S] |
| PDB | scop | BSM | RELI Base |
Header | 
¹ |
|---|---|---|---|---|---|
| 1alo | 1alo | 1alo | 1alo | Aldehyde oxidoreductase (complex with isopropyl alcohol, Cl¯ and Mg2+); Desulfovibrio gigas | MS6CD10 |
¹ Macromolecular Structures abstract.
Full text is available to BioMedNet
Members
References
|
Bibliography on structural studies of xanthine oxidase family |
