2HUO

Crystal structure of mouse myo-inositol oxygenase in complex with substrate

Summary for 2HUO

• Entry DOI: 10.2210/pdb2huo/pdb
• Descriptor: Inositol oxygenase, FE (III) ION, HYDROXIDE ION, ... (6 entities in total)
• Functional Keywords: protein-substrate complex, hd domain fold, oxidoreductase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm (By similarity): Q9QXN5
• Total number of polymer chains: 1
• Total formula weight: 33870.77

Authors

Brown, P.M.,Caradoc-Davies, T.T.,Dickson, J.M.J.,Cooper, G.J.S.,Loomes, K.M.,Baker, E.N. (deposition date: 2006-07-27, release date: 2006-09-26, Last modification date: 2024-02-14)

Primary citation

Brown, P.M.,Caradoc-Davies, T.T.,Dickson, J.M.,Cooper, G.J.,Loomes, K.M.,Baker, E.N.
Crystal structure of a substrate complex of myo-inositol oxygenase, a di-iron oxygenase with a key role in inositol metabolism.
Proc.Natl.Acad.Sci.Usa, 103:15032-15037, 2006

PubMed Abstract: Altered metabolism of the inositol sugars myo-inositol (MI) and d-chiro-inositol is implicated in diabetic complications. In animals, catabolism of MI and D-chiro-inositol depends on the enzyme MI oxygenase (MIOX), which catalyzes the first committed step of the glucuronate-xylulose pathway, and is found almost exclusively in the kidneys. The crystal structure of MIOX, in complex with MI, has been determined by multiwavelength anomalous diffraction methods and refined at 2.0-A resolution (R=0.206, Rfree=0.253). The structure reveals a monomeric, single-domain protein with a mostly helical fold that is distantly related to the diverse HD domain superfamily. Five helices form the structural core and provide six ligands (four His and two Asp) for the di-iron center, in which the two iron atoms are bridged by a putative hydroxide ion and one of the Asp ligands, Asp-124. A key loop forms a lid over the MI substrate, which is coordinated in bidentate mode to one iron atom. It is proposed that this mode of iron coordination, and interaction with a key Lys residue, activate MI for bond cleavage. The structure also reveals the basis of substrate specificity and suggests routes for the development of specific MIOX inhibitors.

PubMed: 17012379
DOI: 10.1073/pnas.0605143103

Experimental method

X-RAY DIFFRACTION (2 Å)