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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. | |||
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> | |||
<div class="pdbe-citations 1jrp" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Xanthine dehydrogenase 3D structures|Xanthine dehydrogenase 3D structures]] | |||
[[Category: | == 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]] | ||
Latest revision as of 09:51, 30 October 2024
Crystal Structure of Xanthine Dehydrogenase inhibited by alloxanthine from Rhodobacter capsulatusCrystal Structure of Xanthine Dehydrogenase inhibited by alloxanthine from Rhodobacter capsulatus
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedXanthine 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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