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| | <StructureSection load='2qxx' size='340' side='right'caption='[[2qxx]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2qxx' size='340' side='right'caption='[[2qxx]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qxx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QXX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qxx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QXX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qlp|2qlp]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dcd ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dCTP_deaminase dCTP deaminase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.13 3.5.4.13] </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=2qxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qxx OCA], [https://pdbe.org/2qxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qxx RCSB], [https://www.ebi.ac.uk/pdbsum/2qxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qxx 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=2qxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qxx OCA], [https://pdbe.org/2qxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qxx RCSB], [https://www.ebi.ac.uk/pdbsum/2qxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qxx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DCDB_MYCTU DCDB_MYCTU] Bifunctional enzyme that catalyzes both the deamination of dCTP to dUTP and the hydrolysis of dUTP to dUMP without releasing the toxic dUTP intermediate. It also acts as a dUTP diphosphatase. Affinity for dCTP and dUTP are very similar.<ref>PMID:18164314</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: DCTP deaminase]]
| + | [[Category: Christophersen S]] |
| - | [[Category: Christophersen, S]] | + | [[Category: Harris P]] |
| - | [[Category: Harris, P]] | + | [[Category: Willemoes M]] |
| - | [[Category: Willemoes, M]] | + | |
| - | [[Category: Distorted beta barrel]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nucleotide metabolism]]
| + | |
| Structural highlights
Function
DCDB_MYCTU Bifunctional enzyme that catalyzes both the deamination of dCTP to dUTP and the hydrolysis of dUTP to dUMP without releasing the toxic dUTP intermediate. It also acts as a dUTP diphosphatase. Affinity for dCTP and dUTP are very similar.[1]
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
Recombinant deoxycytidine triphosphate (dCTP) deaminase from Mycobacterium tuberculosis was produced in Escherichia coli and purified. The enzyme proved to be a bifunctional dCTP deaminase:deoxyuridine triphosphatase. As such, the M. tuberculosis enzyme is the second bifunctional enzyme to be characterised and provides evidence for bifunctionality of dCTP deaminase occurring outside the Archaea kingdom. A steady-state kinetic analysis revealed that the affinity for dCTP and deoxyuridine triphosphate as substrates for the synthesis of deoxyuridine monophosphate were very similar, a result that contrasts that obtained previously for the archaean Methanocaldococcus jannaschii enzyme, which showed approximately 10-fold lower affinity for deoxyuridine triphosphate than for dCTP. The crystal structures of the enzyme in complex with the inhibitor, thymidine triphosphate, and the apo form have been solved. Comparison of the two shows that upon binding of thymidine triphosphate, the disordered C-terminal arranges as a lid covering the active site, and the enzyme adapts an inactive conformation as a result of structural changes in the active site. In the inactive conformation dephosphorylation cannot take place due to the absence of a water molecule otherwise hydrogen-bonded to O2 of the alpha-phosphate.
Mechanism of dTTP inhibition of the bifunctional dCTP deaminase:dUTPase encoded by Mycobacterium tuberculosis.,Helt SS, Thymark M, Harris P, Aagaard C, Dietrich J, Larsen S, Willemoes M J Mol Biol. 2008 Feb 15;376(2):554-69. Epub 2007 Dec 5. PMID:18164314[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Helt SS, Thymark M, Harris P, Aagaard C, Dietrich J, Larsen S, Willemoes M. Mechanism of dTTP inhibition of the bifunctional dCTP deaminase:dUTPase encoded by Mycobacterium tuberculosis. J Mol Biol. 2008 Feb 15;376(2):554-69. Epub 2007 Dec 5. PMID:18164314 doi:http://dx.doi.org/10.1016/j.jmb.2007.11.099
- ↑ Helt SS, Thymark M, Harris P, Aagaard C, Dietrich J, Larsen S, Willemoes M. Mechanism of dTTP inhibition of the bifunctional dCTP deaminase:dUTPase encoded by Mycobacterium tuberculosis. J Mol Biol. 2008 Feb 15;376(2):554-69. Epub 2007 Dec 5. PMID:18164314 doi:http://dx.doi.org/10.1016/j.jmb.2007.11.099
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