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| | ==Crystal structure of thymidine kinase from Herpes simplex virus type 1 in complex with N-methyl-DHBT== | | ==Crystal structure of thymidine kinase from Herpes simplex virus type 1 in complex with N-methyl-DHBT== |
| - | <StructureSection load='3f0t' size='340' side='right' caption='[[3f0t]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3f0t' size='340' side='right'caption='[[3f0t]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3f0t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-1 Hhv-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F0T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3f0t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1_strain_17 Human alphaherpesvirus 1 strain 17]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F0T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NCV:N-METHYL-6-(1,3-DIHYDROXY-ISOBUTYL)THYMINE'>NCV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">[[1e2p|1e2p]], [[1e2h|1e2h]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCV:N-METHYL-6-(1,3-DIHYDROXY-ISOBUTYL)THYMINE'>NCV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TK, UL23 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10299 HHV-1])</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=3f0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f0t OCA], [https://pdbe.org/3f0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f0t RCSB], [https://www.ebi.ac.uk/pdbsum/3f0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f0t ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidine_kinase Thymidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.21 2.7.1.21] </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=3f0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f0t OCA], [http://pdbe.org/3f0t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f0t RCSB], [http://www.ebi.ac.uk/pdbsum/3f0t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f0t ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KITH_HHV11 KITH_HHV11]] In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome (By similarity). | + | [https://www.uniprot.org/uniprot/KITH_HHV11 KITH_HHV11] In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome (By similarity). |
| | == 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== |
| - | *[[Thymidine kinase|Thymidine kinase]] | + | *[[Thymidine kinase 3D structures|Thymidine kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hhv-1]] | + | [[Category: Human alphaherpesvirus 1 strain 17]] |
| - | [[Category: Thymidine kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Ametamey, S]] | + | [[Category: Ametamey S]] |
| - | [[Category: Martic, M]] | + | [[Category: Martic M]] |
| - | [[Category: Pernot, L]] | + | [[Category: Pernot L]] |
| - | [[Category: Perozzo, R]] | + | [[Category: Perozzo R]] |
| - | [[Category: Scapozza, L]] | + | [[Category: Scapozza L]] |
| - | [[Category: Westermaier, Y]] | + | [[Category: Westermaier Y]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Dna synthesis]]
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| - | [[Category: Dna-synthesis]]
| + | |
| - | [[Category: Early protein]]
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| - | [[Category: Nucleotide-binding]]
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| - | [[Category: Pet tracer]]
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| - | [[Category: Transferase]]
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| Structural highlights
Function
KITH_HHV11 In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome (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
Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to "gold standard" 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (K(m) = 10 +/- 0.3 muM; k(cat) = 0.036 +/- 0.015 sec(-1)). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues.
Synthesis, crystal structure, and in vitro biological evaluation of C-6 pyrimidine derivatives: new lead structures for monitoring gene expression in vivo.,Martic M, Pernot L, Westermaier Y, Perozzo R, Kraljevic TG, Kristafor S, Raic-Malic S, Scapozza L, Ametamey S Nucleosides Nucleotides Nucleic Acids. 2011 Apr;30(4):293-315. PMID:21623543[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martic M, Pernot L, Westermaier Y, Perozzo R, Kraljevic TG, Kristafor S, Raic-Malic S, Scapozza L, Ametamey S. Synthesis, crystal structure, and in vitro biological evaluation of C-6 pyrimidine derivatives: new lead structures for monitoring gene expression in vivo. Nucleosides Nucleotides Nucleic Acids. 2011 Apr;30(4):293-315. PMID:21623543 doi:10.1080/15257770.2011.581258
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