|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| - | ==THE CRYSTAL STRUCTURE OF LEISHMANIA MAJOR DUTPASE IN COMPLEX DUMP== | + | ==The Crystal Structure of Leishmania major dUTPase in complex dUMP== |
| - | <StructureSection load='2yaz' size='340' side='right' caption='[[2yaz]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='2yaz' size='340' side='right'caption='[[2yaz]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2yaz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leima Leima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YAZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YAZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2yaz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YAZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2yay|2yay]], [[2yb0|2yb0]], [[2cje|2cje]], [[2cic|2cic]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </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=2yaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yaz OCA], [https://pdbe.org/2yaz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yaz RCSB], [https://www.ebi.ac.uk/pdbsum/2yaz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yaz ProSAT]</span></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=2yaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yaz OCA], [http://pdbe.org/2yaz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yaz RCSB], [http://www.ebi.ac.uk/pdbsum/2yaz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yaz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/O15826_LEIMA O15826_LEIMA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 21: |
| | | | |
| | ==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: Leima]] | + | [[Category: Large Structures]] |
| - | [[Category: DUTP diphosphatase]] | + | [[Category: Leishmania major]] |
| - | [[Category: Bosch-Navarrete, C]] | + | [[Category: Bosch-Navarrete C]] |
| - | [[Category: Fogg, M J]] | + | [[Category: Fogg MJ]] |
| - | [[Category: Gonzalez-Pacanowska, D]] | + | [[Category: Gonzalez-Pacanowska D]] |
| - | [[Category: Hemsworth, G R]] | + | [[Category: Hemsworth GR]] |
| - | [[Category: Moroz, O V]] | + | [[Category: Moroz OV]] |
| - | [[Category: Scott, B]] | + | [[Category: Scott B]] |
| - | [[Category: Wilson, K S]] | + | [[Category: Wilson KS]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Leishmaniasis]]
| + | |
| Structural highlights
Function
O15826_LEIMA
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
|
