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'''Crystal structure of Human myo-Inositol Oxygenase (MIOX)''' | '''Crystal structure of Human myo-Inositol Oxygenase (MIOX)''' | ||
==Overview== | |||
Altered inositol metabolism is implicated in a number of diabetic complications. The first committed step in mammalian inositol catabolism is performed by myo-inositol oxygenase (MIOX), which catalyzes a unique four-electron dioxygen-dependent ring cleavage of myo-inositol to d-glucuronate. Here, we present the crystal structure of human MIOX in complex with myo-inosose-1 bound in a terminal mode to the MIOX diiron cluster site. Furthermore, from biochemical and biophysical results from N-terminal deletion mutagenesis we show that the N terminus is important, through coordination of a set of loops covering the active site, in shielding the active site during catalysis. EPR spectroscopy of the unliganded enzyme displays a two-component spectrum that we can relate to an open and a closed active site conformation. Furthermore, based on site-directed mutagenesis in combination with biochemical and biophysical data, we propose a novel role for Lys(127) in governing access to the diiron cluster. | |||
==About this Structure== | ==About this Structure== | ||
2IBN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IBN OCA]. | 2IBN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IBN OCA]. | ||
==Reference== | |||
Structural and Biophysical Characterization of Human myo-Inositol Oxygenase., Thorsell AG, Persson C, Voevodskaya N, Busam RD, Hammarstrom M, Graslund S, Graslund A, Hallberg BM, J Biol Chem. 2008 May 30;283(22):15209-16. Epub 2008 Mar 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18364358 18364358] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Inositol oxygenase]] | [[Category: Inositol oxygenase]] | ||
| Line 48: | Line 54: | ||
[[Category: Diiron]] | [[Category: Diiron]] | ||
[[Category: Inositol]] | [[Category: Inositol]] | ||
[[Category: Oxidoreductase]] | |||
[[Category: Reductase]] | [[Category: Reductase]] | ||
[[Category: Sgc]] | [[Category: Sgc]] | ||
[[Category: Structural genomic]] | [[Category: Structural genomic]] | ||
[[Category: Structural genomics consortium]] | [[Category: Structural genomics consortium]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:54:16 2008'' | ||
Revision as of 10:54, 11 June 2008
Crystal structure of Human myo-Inositol Oxygenase (MIOX)
OverviewOverview
Altered inositol metabolism is implicated in a number of diabetic complications. The first committed step in mammalian inositol catabolism is performed by myo-inositol oxygenase (MIOX), which catalyzes a unique four-electron dioxygen-dependent ring cleavage of myo-inositol to d-glucuronate. Here, we present the crystal structure of human MIOX in complex with myo-inosose-1 bound in a terminal mode to the MIOX diiron cluster site. Furthermore, from biochemical and biophysical results from N-terminal deletion mutagenesis we show that the N terminus is important, through coordination of a set of loops covering the active site, in shielding the active site during catalysis. EPR spectroscopy of the unliganded enzyme displays a two-component spectrum that we can relate to an open and a closed active site conformation. Furthermore, based on site-directed mutagenesis in combination with biochemical and biophysical data, we propose a novel role for Lys(127) in governing access to the diiron cluster.
About this StructureAbout this Structure
2IBN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural and Biophysical Characterization of Human myo-Inositol Oxygenase., Thorsell AG, Persson C, Voevodskaya N, Busam RD, Hammarstrom M, Graslund S, Graslund A, Hallberg BM, J Biol Chem. 2008 May 30;283(22):15209-16. Epub 2008 Mar 24. PMID:18364358 Page seeded by OCA on Wed Jun 11 10:54:16 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Inositol oxygenase
- Single protein
- Arrowsmith, C.
- Berg, S Van Den.
- Berglund, H.
- Busam, R D.
- Collins, R.
- Edwards, A.
- Ehn, M.
- Flodin, S.
- Flores, A.
- Graslund, S.
- Hallberg, B M.
- Hammarstrom, M.
- Hogbom, M.
- Holmberg-Schiavone, L.
- Johansson, I.
- Karlberg, T.
- Kotenyova, T.
- Nilsson-Ehle, P.
- Nordlund, P.
- Nyman, T.
- Ogg, D.
- Persson, C.
- SGC, Structural Genomics Consortium.
- Sagemark, J.
- Stenmark, P.
- Sundstrom, M.
- Thorsell, A G.
- Uppenberg, J.
- Weigelt, J.
- Diiron
- Inositol
- Oxidoreductase
- Reductase
- Sgc
- Structural genomic
- Structural genomics consortium