View source for 2w55


==Crystal Structure of Xanthine Dehydrogenase (E232Q variant) from Rhodobacter capsulatus in Complex with Hypoxanthine==
<StructureSection load='2w55' size='340' side='right'caption='[[2w55]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2w55]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodobacter_capsulatus Rhodobacter capsulatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2W55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W55 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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HPA:HYPOXANTHINE'>HPA</scene>, <scene name='pdbligand=XAX:{[(5AR,8R,9AR)-2-AMINO-4-OXO-6,7-DI(SULFANYL-KAPPAS)-3,5,5A,8,9A,10-HEXAHYDRO-4H-PYRANO[3,2-G]PTERIDIN-8-YL]METHYL+DIHYDROGENATO(2-)+PHOSPHATE}(HYDROXY)OXO(THIOXO)MOLYBDENUM'>XAX</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=2w55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w55 OCA], [https://pdbe.org/2w55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w55 RCSB], [https://www.ebi.ac.uk/pdbsum/2w55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w55 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/w5/2w55_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=2w55 ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Rhodobacter capsulatus xanthine dehydrogenase (XDH) is an (alphabeta)(2) heterotetrameric cytoplasmic enzyme that resembles eukaryotic xanthine oxidoreductases in respect to both amino acid sequence and structural fold. To obtain a detailed understanding of the mechanism of substrate and inhibitor binding at the active site, we solved crystal structures of R. capsulatus XDH in the presence of its substrates hypoxanthine, xanthine, and the inhibitor pterin-6-aldehyde using either the inactive desulfo form of the enzyme or an active site mutant (E(B)232Q) to prevent substrate turnover. The hypoxanthine- and xanthine-bound structures reveal the orientation of both substrates at the active site and show the importance of residue Glu(B)-232 for substrate positioning. The oxygen atom at the C-6 position of both substrates is oriented toward Arg(B)-310 in the active site. Thus the substrates bind in an orientation opposite to the one seen in the structure of the reduced enzyme with the inhibitor oxypurinol. The tightness of the substrates in the active site suggests that the intermediate products must exit the binding pocket to allow first the attack of the C-2, followed by oxidation of the C-8 atom to form the final product uric acid. Structural studies of pterin-6-aldehyde, a potent inhibitor of R. capsulatus XDH, contribute further to the understanding of the relative positioning of inhibitors and substrates in the binding pocket. Steady state kinetics reveal a competitive inhibition pattern with a K(i) of 103.57 +/- 18.96 nm for pterin-6-aldehyde.

Mechanism of Substrate and Inhibitor Binding of Rhodobacter capsulatus Xanthine Dehydrogenase.,Dietzel U, Kuper J, Doebbler JA, Schulte A, Truglio JJ, Leimkuhler S, Kisker C J Biol Chem. 2009 Mar 27;284(13):8768-76. Epub 2008 Dec 24. PMID:19109249<ref>PMID:19109249</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2w55" style="background-color:#fffaf0;"></div>

==See Also==
*[[Xanthine dehydrogenase 3D structures|Xanthine dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rhodobacter capsulatus]]
[[Category: Doebbler JA]]
[[Category: Kisker C]]
[[Category: Leimkuhler S]]
[[Category: Truglio JJ]]