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| | ==Allantoin racemase from Klebsiella pneumoniae== | | ==Allantoin racemase from Klebsiella pneumoniae== |
| - | <StructureSection load='3qvk' size='340' side='right' caption='[[3qvk]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3qvk' size='340' side='right'caption='[[3qvk]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qvk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Klep7 Klep7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QVK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QVK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qvk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klep7 Klep7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QVK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2AL:1-(2,5-DIOXO-2,5-DIHYDRO-1H-IMIDAZOL-4-YL)UREA'>2AL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2AL:1-(2,5-DIOXO-2,5-DIHYDRO-1H-IMIDAZOL-4-YL)UREA'>2AL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HpxA, KPN78578_17580, KPN_01788 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272620 KLEP7])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HpxA, KPN78578_17580, KPN_01788 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272620 KLEP7])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qvk OCA], [http://pdbe.org/3qvk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qvk RCSB], [http://www.ebi.ac.uk/pdbsum/3qvk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qvk ProSAT]</span></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=3qvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qvk OCA], [https://pdbe.org/3qvk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qvk RCSB], [https://www.ebi.ac.uk/pdbsum/3qvk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qvk ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Klep7]] | | [[Category: Klep7]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ealick, S E]] | | [[Category: Ealick, S E]] |
| | [[Category: French, J B]] | | [[Category: French, J B]] |
| Structural highlights
Publication Abstract from PubMed
The oxidative catabolism of uric acid produces 5-hydroxyisourate (HIU), which is further degraded to (S)-allantoin by two enzymes, HIU hydrolase and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase. The intermediates of the latter two reactions, HIU and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, are unstable in solution and decay nonstereospecifically to allantoin. In addition, nonenzymatic racemization of allantoin has been shown to occur at physiological pH. Since the further breakdown of allantoin is catalyzed by allantoinase, an enzyme that is specific for (S)-allantoin, an allantoin racemase is necessary for complete and efficient catabolism of uric acid. In this work, we characterize the structure and activity of allantoin racemase from Klebsiella pneumoniae (KpHpxA). In addition to an unliganded structure solved using selenomethionyl single-wavelength anomalous dispersion, structures of C79S/C184S KpHpxA in complex with allantoin and with 5-acetylhydantoin are presented. These structures reveal several important features of the active site including an oxyanion hole and a polar binding pocket that interacts with the ureido tail of allantoin and serves to control the orientation of the hydantoin ring. The ability of KpHpxA to interconvert the (R)- and (S)-enantiomers of allantoin is demonstrated, and analysis of the steady-state kinetics of KpHpxA yielded a k(cat)/K(m) of 6.0x10(5) M(-1) s(-1). Mutation of either of the active-site cysteines, Cys79 or Cys184, to serine inactivates this enzyme. The data presented provide new insights into the activity and substrate specificity of this enzyme and enable us to propose a mechanism for catalysis that is consistent with the two-base mechanism observed in other members of the aspartate/glutamate family.
Characterization of the Structure and Function of Klebsiella pneumoniae Allantoin Racemase.,French JB, Neau DB, Ealick SE J Mol Biol. 2011 May 17. PMID:21616082[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ French JB, Neau DB, Ealick SE. Characterization of the Structure and Function of Klebsiella pneumoniae Allantoin Racemase. J Mol Biol. 2011 May 17. PMID:21616082 doi:10.1016/j.jmb.2011.05.016
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