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| | <StructureSection load='2v54' size='340' side='right'caption='[[2v54]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='2v54' size='340' side='right'caption='[[2v54]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2v54]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccc Vaccc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V54 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V54 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2v54]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus_Copenhagen Vaccinia virus Copenhagen]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V54 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V54 FirstGlance]. <br> |
| - | </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=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=TYD:THYMIDINE-5-DIPHOSPHATE'>TYD</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"><div style='overflow: auto; max-height: 3em;'>[[2w0s|2w0s]]</div></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=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=TYD:THYMIDINE-5-DIPHOSPHATE'>TYD</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </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=2v54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v54 OCA], [https://pdbe.org/2v54 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v54 RCSB], [https://www.ebi.ac.uk/pdbsum/2v54 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v54 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=2v54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v54 OCA], [https://pdbe.org/2v54 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v54 RCSB], [https://www.ebi.ac.uk/pdbsum/2v54 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v54 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/KTHY_VACCC KTHY_VACCC]] Poxvirus TMP kinase is able to phosphorylate dTMP, dUMP and also dGMP from any purine and pyrimidine nucleoside triphosphate. The large substrate specificity is explained by the presence of a canal connecting the edge of the dimer interface to the TMP base binding pocket, canal not found in the human homolog (By similarity).
| + | [https://www.uniprot.org/uniprot/KTHY_VACCC KTHY_VACCC] Poxvirus TMP kinase is able to phosphorylate dTMP, dUMP and also dGMP from any purine and pyrimidine nucleoside triphosphate. The large substrate specificity is explained by the presence of a canal connecting the edge of the dimer interface to the TMP base binding pocket, canal not found in the human homolog (By similarity). |
| | == 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: Vaccc]] | + | [[Category: Vaccinia virus Copenhagen]] |
| - | [[Category: DTMP kinase]]
| + | [[Category: Agrofoglio LA]] |
| - | [[Category: Agrofoglio, L A]] | + | [[Category: Balzarini J]] |
| - | [[Category: Balzarini, J]] | + | [[Category: Caillat C]] |
| - | [[Category: Caillat, C]] | + | [[Category: Deville-Bonne D]] |
| - | [[Category: Deville-Bonne, D]] | + | [[Category: Meyer P]] |
| - | [[Category: Meyer, P]] | + | [[Category: Pochet S]] |
| - | [[Category: Pochet, S]] | + | [[Category: Topalis D]] |
| - | [[Category: Topalis, D]] | + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Nucleotide biosynthesis]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Poxvirus]]
| + | |
| - | [[Category: Tmp kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KTHY_VACCC Poxvirus TMP kinase is able to phosphorylate dTMP, dUMP and also dGMP from any purine and pyrimidine nucleoside triphosphate. The large substrate specificity is explained by the presence of a canal connecting the edge of the dimer interface to the TMP base binding pocket, canal not found in the human homolog (By similarity).
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
Unlike most DNA viruses, poxviruses replicate in the cytoplasm of host cells. They encode enzymes needed for genome replication and transcription, including their own thymidine and thymidylate kinases. Some herpes viruses encode only 1 enzyme catalyzing both reactions, a peculiarity used for prodrug activation to obtain maximum specificity. We have solved the crystal structures of vaccinia virus thymidylate kinase bound to TDP or brivudin monophosphate. Although the viral and human enzymes have similar sequences (42% identity), they differ in their homodimeric association and active-site geometry. The vaccinia TMP kinase dimer arrangement is orthogonal and not antiparallel as in human enzyme. This different monomer orientation is related to the presence of a canal connecting the edge of the dimer interface to the TMP base binding pocket. Consequently, the pox enzyme accommodates nucleotides with bulkier bases, like brivudin monophosphate and dGMP; these are efficiently phosphorylated and stabilize the enzyme. The brivudin monophosphate-bound structure explains the structural basis for this specificity, opening the way to the rational development of specific antipox agents that may also be suitable for poxvirus TMP kinase gene-based chemotherapy of cancer.
Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy.,Caillat C, Topalis D, Agrofoglio LA, Pochet S, Balzarini J, Deville-Bonne D, Meyer P Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16900-5. Epub 2008 Oct 29. PMID:18971333[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Caillat C, Topalis D, Agrofoglio LA, Pochet S, Balzarini J, Deville-Bonne D, Meyer P. Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16900-5. Epub 2008 Oct 29. PMID:18971333
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