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| | ==Crystal structure of thymidine kinase from herpes simplex virus type 1 in complex with N-METHYL-FHBT== | | ==Crystal structure of thymidine kinase from herpes simplex virus type 1 in complex with N-METHYL-FHBT== |
| - | <StructureSection load='3rdp' size='340' side='right' caption='[[3rdp]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3rdp' size='340' side='right'caption='[[3rdp]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rdp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Herpes_simplex_virus_(type_1_/_strain_17) Herpes simplex virus (type 1 / strain 17)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RDP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rdp]] 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=3RDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RDP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NMF:6-[(2R)-2-(FLUOROMETHYL)-3-HYDROXY-PROPYL]-1,5-DIMETHYL-PYRIMIDINE-2,4-DIONE'>NMF</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]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f0t|3f0t]], [[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=NMF:6-[(2R)-2-(FLUOROMETHYL)-3-HYDROXY-PROPYL]-1,5-DIMETHYL-PYRIMIDINE-2,4-DIONE'>NMF</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 Herpes simplex virus (type 1 / strain 17)])</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=3rdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rdp OCA], [https://pdbe.org/3rdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rdp RCSB], [https://www.ebi.ac.uk/pdbsum/3rdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rdp 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=3rdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rdp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rdp RCSB], [http://www.ebi.ac.uk/pdbsum/3rdp PDBsum]</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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3rdp" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==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: Thymidine kinase]] | + | [[Category: Human alphaherpesvirus 1 strain 17]] |
| - | [[Category: Ametamey, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Martic, M]] | + | [[Category: Ametamey S]] |
| - | [[Category: Pernot, L]] | + | [[Category: Martic M]] |
| - | [[Category: Perozzo, R]] | + | [[Category: Pernot L]] |
| - | [[Category: Scapozza, L]] | + | [[Category: Perozzo R]] |
| - | [[Category: Westermaier, Y]] | + | [[Category: Scapozza L]] |
| - | [[Category: Atp-binding]]
| + | [[Category: Westermaier Y]] |
| - | [[Category: Dna synthesis]]
| + | |
| - | [[Category: Dna-synthesis]]
| + | |
| - | [[Category: Early protein]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Pet tracer]]
| + | |
| - | [[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).
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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