3bxd

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[[Image:3bxd.jpg|left|200px]]<br /><applet load="3bxd" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="3bxd, resolution 2.000&Aring;" />
 
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'''Crystal structure of Mouse Myo-inositol oxygenase (re-refined)'''<br />
 
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==Overview==
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==Crystal structure of Mouse Myo-inositol oxygenase (re-refined)==
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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.
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<StructureSection load='3bxd' size='340' side='right'caption='[[3bxd]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3bxd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BXD FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=INS:1,2,3,4,5,6-HEXAHYDROXY-CYCLOHEXANE'>INS</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bxd OCA], [https://pdbe.org/3bxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bxd RCSB], [https://www.ebi.ac.uk/pdbsum/3bxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bxd ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MIOX_MOUSE MIOX_MOUSE]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bx/3bxd_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bxd ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:18364358</ref>
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3BXD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=FE:'>FE</scene>, <scene name='pdbligand=OH:'>OH</scene>, <scene name='pdbligand=INS:'>INS</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol_oxygenase Inositol oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.99.1 1.13.99.1] Known structural/functional Sites: <scene name='pdbsite=AC1:Fe+Binding+Site+For+Residue+A+301'>AC1</scene>, <scene name='pdbsite=AC2:Fe+Binding+Site+For+Residue+A+302'>AC2</scene>, <scene name='pdbsite=AC3:Oh+Binding+Site+For+Residue+A+304'>AC3</scene>, <scene name='pdbsite=AC4:Ins+Binding+Site+For+Residue+A+303'>AC4</scene> and <scene name='pdbsite=AC5:Fmt+Binding+Site+For+Residue+A+305'>AC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BXD OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structure of a substrate complex of myo-inositol oxygenase, a di-iron oxygenase with a key role in inositol metabolism., Brown PM, Caradoc-Davies TT, Dickson JM, Cooper GJ, Loomes KM, Baker EN, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15032-7. Epub 2006 Sep 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17012379 17012379]
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</div>
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[[Category: Inositol oxygenase]]
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<div class="pdbe-citations 3bxd" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Hallberg BM]]
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[[Category: Hallberg, B.M.]]
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[[Category: FE]]
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[[Category: FMT]]
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[[Category: INS]]
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[[Category: OH]]
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[[Category: diiron]]
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[[Category: hd domain fold]]
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[[Category: oxidoreductase]]
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[[Category: protein-substrate complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:15:38 2008''
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Current revision

Crystal structure of Mouse Myo-inositol oxygenase (re-refined)

PDB ID 3bxd

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