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| | ==THE CRYSTAL STRUCTURE OF A COMPLEX OF CAMPYLOBACTER JEJUNI DUTPASE WITH SUBSTRATE ANALOGUE DUPNHPP== | | ==THE CRYSTAL STRUCTURE OF A COMPLEX OF CAMPYLOBACTER JEJUNI DUTPASE WITH SUBSTRATE ANALOGUE DUPNHPP== |
| - | <StructureSection load='2cic' size='340' side='right' caption='[[2cic]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='2cic' size='340' side='right'caption='[[2cic]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cic]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"campylobacter_fetus_subsp._jejuni"_smibert_1974 "campylobacter fetus subsp. jejuni" smibert 1974]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CIC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CIC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cic]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Campylobacter_jejuni Campylobacter jejuni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CIC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1w2y|1w2y]], [[2yay|2yay]], [[2cje|2cje]], [[2yaz|2yaz]], [[2yb0|2yb0]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=2cic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cic OCA], [http://pdbe.org/2cic PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cic RCSB], [http://www.ebi.ac.uk/pdbsum/2cic PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2cic 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=2cic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cic OCA], [https://pdbe.org/2cic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cic RCSB], [https://www.ebi.ac.uk/pdbsum/2cic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cic ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q0P8G4_CAMJE Q0P8G4_CAMJE] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Deoxyuridine 5'-triphosphate nucleotidohydrolase|Deoxyuridine 5'-triphosphate nucleotidohydrolase]] | + | *[[DUTPase 3D structures|DUTPase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Campylobacter fetus subsp. jejuni smibert 1974]] | + | [[Category: Campylobacter jejuni]] |
| - | [[Category: Gonzalez-Pacanowska, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Harkiolaki, M]] | + | [[Category: Gonzalez-Pacanowska D]] |
| - | [[Category: Moroz, O V]] | + | [[Category: Harkiolaki M]] |
| - | [[Category: Wilson, K S]] | + | [[Category: Moroz OV]] |
| - | [[Category: Drug target]]
| + | [[Category: Wilson KS]] |
| - | [[Category: Dutp pyrophosphatase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Ligand complex]]
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| Structural highlights
Function
Q0P8G4_CAMJE
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Members of the Leishmania genus are the causative agents of the life-threatening disease leishmaniasis. New drugs are being sought due to increasing resistance and adverse side effects with current treatments. The knowledge that dUTPase is an essential enzyme and that the all alpha-helical dimeric kinetoplastid dUTPases have completely different structures compared with the trimeric beta-sheet type dUTPase possessed by most organisms, including humans, make the dimeric enzymes attractive drug targets. Here, we present crystal structures of the Leishmania major dUTPase in complex with substrate analogues, the product dUMP and a substrate fragment, and of the homologous Campylobacter jejuni dUTPase in complex with a triphosphate substrate analogue. The metal-binding properties of both enzymes are shown to be dependent upon the ligand identity, a previously unseen characteristic of this family. Furthermore, structures of the Leishmania enzyme in the presence of dUMP and deoxyuridine coupled with tryptophan fluorescence quenching indicate that occupation of the phosphate binding region is essential for induction of the closed conformation and hence for substrate binding. These findings will aid in the development of dUTPase inhibitors as potential new lead anti-trypanosomal compounds.
The Crystal Structure of the Leishmania major Deoxyuridine Triphosphate Nucleotidohydrolase in Complex with Nucleotide Analogues, dUMP, and Deoxyuridine.,Hemsworth GR, Moroz OV, Fogg MJ, Scott B, Bosch-Navarrete C, Gonzalez-Pacanowska D, Wilson KS J Biol Chem. 2011 May 6;286(18):16470-81. Epub 2011 Mar 15. PMID:21454646[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hemsworth GR, Moroz OV, Fogg MJ, Scott B, Bosch-Navarrete C, Gonzalez-Pacanowska D, Wilson KS. The Crystal Structure of the Leishmania major Deoxyuridine Triphosphate Nucleotidohydrolase in Complex with Nucleotide Analogues, dUMP, and Deoxyuridine. J Biol Chem. 2011 May 6;286(18):16470-81. Epub 2011 Mar 15. PMID:21454646 doi:10.1074/jbc.M111.224873
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