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== | ==Crystal Structure of Xanthine Dehydrogenase inhibited by alloxanthine from Rhodobacter capsulatus== | ||
<StructureSection load='1jrp' size='340' side='right'caption='[[1jrp]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1jrp]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodobacter_capsulatus Rhodobacter capsulatus]. 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=1JRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JRP 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]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=141:OXYPURINOL'>141</scene>, <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=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></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=1jrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jrp OCA], [https://pdbe.org/1jrp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jrp RCSB], [https://www.ebi.ac.uk/pdbsum/1jrp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jrp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/O54050_RHOCA O54050_RHOCA] | |||
== 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/jr/1jrp_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=1jrp ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Xanthine dehydrogenase (XDH), a complex molybdo/iron-sulfur/flavoprotein, catalyzes the oxidation of hypoxanthine to xanthine followed by oxidation of xanthine to uric acid with concomitant reduction of NAD+. The 2.7 A resolution structure of Rhodobacter capsulatus XDH reveals that the bacterial and bovine XDH have highly similar folds despite differences in subunit composition. The NAD+ binding pocket of the bacterial XDH resembles that of the dehydrogenase form of the bovine enzyme rather than that of the oxidase form, which reduces O(2) instead of NAD+. The drug allopurinol is used to treat XDH-catalyzed uric acid build-up occurring in gout or during cancer chemotherapy. As a hypoxanthine analog, it is oxidized to alloxanthine, which cannot be further oxidized but acts as a tight binding inhibitor of XDH. The 3.0 A resolution structure of the XDH-alloxanthine complex shows direct coordination of alloxanthine to the molybdenum via a nitrogen atom. These results provide a starting point for the rational design of new XDH inhibitors. | Xanthine dehydrogenase (XDH), a complex molybdo/iron-sulfur/flavoprotein, catalyzes the oxidation of hypoxanthine to xanthine followed by oxidation of xanthine to uric acid with concomitant reduction of NAD+. The 2.7 A resolution structure of Rhodobacter capsulatus XDH reveals that the bacterial and bovine XDH have highly similar folds despite differences in subunit composition. The NAD+ binding pocket of the bacterial XDH resembles that of the dehydrogenase form of the bovine enzyme rather than that of the oxidase form, which reduces O(2) instead of NAD+. The drug allopurinol is used to treat XDH-catalyzed uric acid build-up occurring in gout or during cancer chemotherapy. As a hypoxanthine analog, it is oxidized to alloxanthine, which cannot be further oxidized but acts as a tight binding inhibitor of XDH. The 3.0 A resolution structure of the XDH-alloxanthine complex shows direct coordination of alloxanthine to the molybdenum via a nitrogen atom. These results provide a starting point for the rational design of new XDH inhibitors. | ||
Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus.,Truglio JJ, Theis K, Leimkuhler S, Rappa R, Rajagopalan KV, Kisker C Structure. 2002 Jan;10(1):115-25. PMID:11796116<ref>PMID:11796116</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1jrp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Xanthine dehydrogenase 3D structures|Xanthine dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: RCSB PDB Molecule of the Month]] | |||
[[Category: Rhodobacter capsulatus]] | [[Category: Rhodobacter capsulatus]] | ||
[[Category: Xanthine | [[Category: Xanthine Oxidoreductase]] | ||
[[Category: Kisker | [[Category: Kisker C]] | ||
[[Category: Leimkuhler | [[Category: Leimkuhler S]] | ||
[[Category: Rajagopalan | [[Category: Rajagopalan KV]] | ||
[[Category: Rappa | [[Category: Rappa R]] | ||
[[Category: Theis | [[Category: Theis K]] | ||
[[Category: Truglio | [[Category: Truglio JJ]] | ||