Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Crystal Structure of a Substrate Complex of myo-Inositol Oxygenase, a Di-Iron Oxygenase with a Key Role in Inositol Metabolism

Peter M. Brown, Tom T. Caradoc-Davies, James M. J. Dickson, Garth J. S. Cooper, Kerry M. Loomes and Edward N. Baker
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 41 (Oct. 10, 2006), pp. 15032-15037
Stable URL: http://www.jstor.org/stable/30051497
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Crystal Structure of a Substrate Complex of myo-Inositol Oxygenase, a Di-Iron Oxygenase with a Key Role in Inositol Metabolism
Preview not available

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-Å resolution (R = 0.206, $R_{free} = 0.253$). 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.

Page Thumbnails

  • Thumbnail: Page 
15032
    15032
  • Thumbnail: Page 
15033
    15033
  • Thumbnail: Page 
15034
    15034
  • Thumbnail: Page 
15035
    15035
  • Thumbnail: Page 
15036
    15036
  • Thumbnail: Page 
15037
    15037