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| | <StructureSection load='1osn' size='340' side='right'caption='[[1osn]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='1osn' size='340' side='right'caption='[[1osn]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1osn]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-3 Hhv-3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1osn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_3 Human alphaherpesvirus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OSN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BVP:(E)-5-(2-BROMOVINYL)-2-DEOXYURIDINE-5-MONOPHOSPHATE'>BVP</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]] 3.2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BVP:(E)-5-(2-BROMOVINYL)-2-DEOXYURIDINE-5-MONOPHOSPHATE'>BVP</scene></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=1osn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osn OCA], [http://pdbe.org/1osn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osn RCSB], [http://www.ebi.ac.uk/pdbsum/1osn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1osn 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=1osn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osn OCA], [https://pdbe.org/1osn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1osn RCSB], [https://www.ebi.ac.uk/pdbsum/1osn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1osn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KITH_VZVO KITH_VZVO]] 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_VZVO KITH_VZVO] 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-3]] | + | [[Category: Human alphaherpesvirus 3]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thymidine kinase]]
| + | [[Category: Balzarini J]] |
| - | [[Category: Balzarini, J]] | + | [[Category: Bird LE]] |
| - | [[Category: Bird, L E]] | + | [[Category: Degreve B]] |
| - | [[Category: Degreve, B]] | + | [[Category: Leslie KD]] |
| - | [[Category: Leslie, K D]] | + | [[Category: Ren J]] |
| - | [[Category: Ren, J]] | + | [[Category: Stammers DK]] |
| - | [[Category: Stammers, D K]] | + | [[Category: Wright A]] |
| - | [[Category: Wright, A]] | + | |
| - | [[Category: Bvdu-mp]]
| + | |
| - | [[Category: Chickenpox]]
| + | |
| - | [[Category: Human herpes virus 3]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
KITH_VZVO 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
Herpes virus thymidine kinases are responsible for the activation of nucleoside antiviral drugs including (E)-5-(2-bromovinyl)-2'-deoxyuridine. Such viral thymidine kinases (tk), beside having a broader substrate specificity compared with host cell enzymes, also show significant variation in nucleoside phosphorylation among themselves. We have determined the crystal structure of Varicella zoster virus (VZV, human herpes virus 3) thymidine kinase complexed with (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate and ADP. Differences in the conformation of a loop region (residues 55-61) and the position of two alpha-helices at the subunit interface of VZV-tk compared with the herpes simplex virus type 1 (human herpes virus 1) enzyme give rise to changes in the positioning of residues such as tyrosine 66 and glutamine 90, which hydrogen bond to the substrate in the active site. Such changes in combination with the substitution in VZV-tk of two phenylalanine residues (in place of a tyrosine and methionine), which sandwich the substrate pyrimidine ring, cause an alteration in the positioning of the base. The interaction of the (E)-5-(2-bromovinyl)-2'-deoxyuridine deoxyribose ring with the protein is altered by substitution of tyrosine 21 and phenylalanine 139 (analagous to herpes simplex virus type 1 histidine 58 and tyrosine 172), which may explain some of the differences in nucleoside sugar selectivity between both enzymes. The altered active site architecture may also account for the differences in the substrate activity of ganciclovir for the two thymidine kinases. These data should be of use in the design of novel antiherpes and antitumor drugs.
Crystal structure of varicella zoster virus thymidine kinase.,Bird LE, Ren J, Wright A, Leslie KD, Degreve B, Balzarini J, Stammers DK J Biol Chem. 2003 Jul 4;278(27):24680-7. Epub 2003 Apr 9. PMID:12686543[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bird LE, Ren J, Wright A, Leslie KD, Degreve B, Balzarini J, Stammers DK. Crystal structure of varicella zoster virus thymidine kinase. J Biol Chem. 2003 Jul 4;278(27):24680-7. Epub 2003 Apr 9. PMID:12686543 doi:10.1074/jbc.M302025200
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