2j87: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /> <applet load="2j87" size="450" color="white" frame="true" align="right" spinBox="true" caption="2j87, resolution 3.10Å" /> '''STRUCTURE OF VACCIN... |
No edit summary |
||
| (24 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Structure of vaccinia virus thymidine kinase in complex with dTTP: insights for drug design== | ||
<StructureSection load='2j87' size='340' side='right'caption='[[2j87]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
[[Category: | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2j87]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J87 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J87 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</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=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2j87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j87 OCA], [https://pdbe.org/2j87 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j87 RCSB], [https://www.ebi.ac.uk/pdbsum/2j87 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j87 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KITH_VACCA KITH_VACCA] Phosphorylates thymidine and thymidine analogs, such as azidothymidine (AZT). Part of the salvage pathway for pyrimidine deoxyribonucleotide synthesis. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j8/2j87_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j87 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: Development of countermeasures to bioterrorist threats such as those posed by the smallpox virus (variola), include vaccination and drug development. Selective activation of nucleoside analogues by virus-encoded thymidine (dThd) kinases (TK) represents one of the most successful strategies for antiviral chemotherapy as demonstrated for anti-herpes drugs. Vaccinia virus TK is a close orthologue of variola TK but also shares a relatively high sequence identity to human type 2 TK (hTK), thus achieving drug selectivity relative to the host enzyme is challenging. RESULTS: In order to identify any differences compared to hTK that may be exploitable in drug design, we have determined the crystal structure of VVTK, in complex with thymidine 5'-triphosphate (dTTP). Although most of the active site residues are conserved between hTK and VVTK, we observe a difference in conformation of residues Asp-43 and Arg-45. The equivalent residues in hTK hydrogen bond to dTTP, whereas in subunit D of VVTK, Asp-43 and Arg-45 adopt a different conformation preventing interaction with this nucleotide. Asp-43 and Arg-45 are present in a flexible loop, which is disordered in subunits A, B and C. The observed difference in conformation and flexibility may also explain the ability of VVTK to phosphorylate (South)-methanocarbathymine whereas, in contrast, no substrate activity with hTK is reported for this compound. CONCLUSION: The difference in conformation for Asp-43 and Arg-45 could thus be used in drug design to generate VVTK/Variola TK-selective nucleoside analogue substrates and/or inhibitors that have lower affinity for hTK. | |||
Structure of vaccinia virus thymidine kinase in complex with dTTP: insights for drug design.,El Omari K, Solaroli N, Karlsson A, Balzarini J, Stammers DK BMC Struct Biol. 2006 Oct 24;6:22. PMID:17062140<ref>PMID:17062140</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2j87" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thymidine kinase 3D structures|Thymidine kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Vaccinia virus]] | [[Category: Vaccinia virus]] | ||
[[Category: Balzarini | [[Category: Balzarini J]] | ||
[[Category: | [[Category: El Omari K]] | ||
[[Category: | [[Category: Karlsson A]] | ||
[[Category: Solaroli | [[Category: Solaroli N]] | ||
[[Category: Stammers | [[Category: Stammers DK]] | ||
