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[[Image:1fo4.gif|left|200px]]
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{{STRUCTURE_1fo4|  PDB=1fo4  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF XANTHINE DEHYDROGENASE ISOLATED FROM BOVINE MILK'''


==CRYSTAL STRUCTURE OF XANTHINE DEHYDROGENASE ISOLATED FROM BOVINE MILK==
<StructureSection load='1fo4' size='340' side='right'caption='[[1fo4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fo4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. The September 2009 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Xanthine Oxidoreductase''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2009_9 10.2210/rcsb_pdb/mom_2009_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FO4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=MTE:PHOSPHONIC+ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER'>MTE</scene>, <scene name='pdbligand=SAL:2-HYDROXYBENZOIC+ACID'>SAL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1fo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fo4 OCA], [https://pdbe.org/1fo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fo4 RCSB], [https://www.ebi.ac.uk/pdbsum/1fo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fo4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/XDH_BOVIN XDH_BOVIN] Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fo/1fo4_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1fo4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mammalian xanthine oxidoreductases, which catalyze the last two steps in the formation of urate, are synthesized as the dehydrogenase form xanthine dehydrogenase (XDH) but can be readily converted to the oxidase form xanthine oxidase (XO) by oxidation of sulfhydryl residues or by proteolysis. Here, we present the crystal structure of the dimeric (M(r), 290,000) bovine milk XDH at 2.1-A resolution and XO at 2.5-A resolution and describe the major changes that occur on the proteolytic transformation of XDH to the XO form. Each molecule is composed of an N-terminal 20-kDa domain containing two iron sulfur centers, a central 40-kDa flavin adenine dinucleotide domain, and a C-terminal 85-kDa molybdopterin-binding domain with the four redox centers aligned in an almost linear fashion. Cleavage of surface-exposed loops of XDH causes major structural rearrangement of another loop close to the flavin ring (Gln 423Lys 433). This movement partially blocks access of the NAD substrate to the flavin adenine dinucleotide cofactor and changes the electrostatic environment of the active site, reflecting the switch of substrate specificity observed for the two forms of this enzyme.


==Overview==
Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion.,Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10723-8. PMID:11005854<ref>PMID:11005854</ref>
Mammalian xanthine oxidoreductases, which catalyze the last two steps in the formation of urate, are synthesized as the dehydrogenase form xanthine dehydrogenase (XDH) but can be readily converted to the oxidase form xanthine oxidase (XO) by oxidation of sulfhydryl residues or by proteolysis. Here, we present the crystal structure of the dimeric (M(r), 290,000) bovine milk XDH at 2.1-A resolution and XO at 2.5-A resolution and describe the major changes that occur on the proteolytic transformation of XDH to the XO form. Each molecule is composed of an N-terminal 20-kDa domain containing two iron sulfur centers, a central 40-kDa flavin adenine dinucleotide domain, and a C-terminal 85-kDa molybdopterin-binding domain with the four redox centers aligned in an almost linear fashion. Cleavage of surface-exposed loops of XDH causes major structural rearrangement of another loop close to the flavin ring (Gln 423Lys 433). This movement partially blocks access of the NAD substrate to the flavin adenine dinucleotide cofactor and changes the electrostatic environment of the active site, reflecting the switch of substrate specificity observed for the two forms of this enzyme.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1FO4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FO4 OCA].
</div>
<div class="pdbe-citations 1fo4" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion., Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF, Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10723-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11005854 11005854]
*[[Xanthine dehydrogenase 3D structures|Xanthine dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Xanthine dehydrogenase]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Eger, B T.]]
[[Category: Xanthine Oxidoreductase]]
[[Category: Enroth, C.]]
[[Category: Eger BT]]
[[Category: Nishino, T.]]
[[Category: Enroth C]]
[[Category: Okamoto, K.]]
[[Category: Nishino T]]
[[Category: Pai, E F.]]
[[Category: Okamoto K]]
[[Category: 2fe-2s iron sulfur center]]
[[Category: Pai EF]]
[[Category: Fad]]
[[Category: Molybdopterin]]
[[Category: Salicylate]]
[[Category: Xanthine dehydrogenase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:33:42 2008''

Latest revision as of 05:58, 13 August 2026

CRYSTAL STRUCTURE OF XANTHINE DEHYDROGENASE ISOLATED FROM BOVINE MILK

1fo4, resolution 2.10Å

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