4hvo

From Proteopedia

1.75 angstrom x-ray crystal structure of cufe reconstituted 3-hydroxyanthranilate-3,4-dioxygenase from cupriavidus metallidurans

PDB ID 4hvo

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Structural highlights

4hvo is a 1 chain structure with sequence from Cupriavidus metallidurans CH34. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.75Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

3HAO_CUPMC Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.[HAMAP-Rule:MF_00825]^[1]

Publication Abstract from PubMed

The rubredoxin motif is present in over 74,000 protein sequences and 2,000 structures, but few have known functions. A secondary, non-catalytic, rubredoxin-like iron site is conserved in 3-hydroxyanthranilate 3,4-dioxygenase (HAO), from single cellular sources but not multicellular sources. Through the population of the two metal binding sites with various metals in bacterial HAO, the structural and functional relationship of the rubredoxin-like site was investigated using kinetic, spectroscopic, crystallographic, and computational approaches. It is shown that the first metal presented preferentially binds to the catalytic site rather than the rubredoxin-like site, which selectively binds iron when the catalytic site is occupied. Furthermore, an iron ion bound to the rubredoxin-like site is readily delivered to an empty catalytic site of metal-free HAO via an intermolecular transfer mechanism. Through the use of metal analysis and catalytic activity measurements, we show that a downstream metabolic intermediate can selectively remove the catalytic iron. As the prokaryotic HAO is often crucial for cell survival, there is a need for ensuring its activity. These results suggest that the rubredoxin-like site is a possible auxiliary iron source to the catalytic center when it is lost during catalysis in a pathway with metabolic intermediates of metal-chelating properties. A spare tire concept is proposed based on this biochemical study, and this concept opens up a potentially new functional paradigm for iron-sulfur centers in iron-dependent enzymes as transient iron binding and shuttling sites to ensure full metal loading of the catalytic site.

An Iron Reservoir to the Catalytic Metal: THE RUBREDOXIN IRON IN AN EXTRADIOL DIOXYGENASE.,Liu F, Geng J, Gumpper RH, Barman A, Davis I, Ozarowski A, Hamelberg D, Liu A J Biol Chem. 2015 Jun 19;290(25):15621-34. doi: 10.1074/jbc.M115.650259. Epub, 2015 Apr 27. PMID:25918158^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Colabroy KL, Zhai H, Li T, Ge Y, Zhang Y, Liu A, Ealick SE, McLafferty FW, Begley TP. The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilate. Biochemistry. 2005 May 31;44(21):7623-31. PMID:15909977 doi:http://dx.doi.org/10.1021/bi0473455
↑ Liu F, Geng J, Gumpper RH, Barman A, Davis I, Ozarowski A, Hamelberg D, Liu A. An Iron Reservoir to the Catalytic Metal: THE RUBREDOXIN IRON IN AN EXTRADIOL DIOXYGENASE. J Biol Chem. 2015 Jun 19;290(25):15621-34. doi: 10.1074/jbc.M115.650259. Epub, 2015 Apr 27. PMID:25918158 doi:http://dx.doi.org/10.1074/jbc.M115.650259