View source for 1e2j


==The nucleoside binding site of Herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography==
<StructureSection load='1e2j' size='340' side='right'caption='[[1e2j]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1e2j]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E2J FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=THM:THYMIDINE'>THM</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kim|1kim]], [[1vtk|1vtk]], [[2vtk|2vtk]], [[3vtk|3vtk]], [[1ki2|1ki2]], [[1ki4|1ki4]], [[1ki5|1ki5]], [[1ki6|1ki6]], [[1ki7|1ki7]], [[1ki8|1ki8]], [[1e2i|1e2i]], [[1e2h|1e2h]], [[1e2k|1e2k]], [[1e2l|1e2l]], [[1e2m|1e2m]], [[1e2n|1e2n]], [[1e2p|1e2p]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymidine_kinase Thymidine kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e2j OCA], [https://pdbe.org/1e2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e2j RCSB], [https://www.ebi.ac.uk/pdbsum/1e2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e2j ProSAT]</span></td></tr>
</table>
== Function ==
[[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 ==
[[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/e2/1e2j_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1e2j ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structures of the full-length Herpes simplex virus type 1 thymidine kinase in its unligated form and in a complex with an adenine analogue have been determined at 1.9 A resolution. The unligated enzyme contains four water molecules in the thymidine pocket and reveals a small induced fit on substrate binding. The structure of the ligated enzyme shows for the first time a bound adenine analogue after numerous complexes with thymine and guanine analogues have been reported. The adenine analogue constitutes a new lead compound for enzyme-prodrug gene therapy. In addition, the structure of mutant Q125N modifying the binding site of the natural substrate thymidine in complex with this substrate has been established at 2.5 A resolution. It reveals that neither the binding mode of thymidine nor the polypeptide backbone conformation is altered, except that the two major hydrogen bonds to thymidine are replaced by a single water-mediated hydrogen bond, which improves the relative acceptance of the prodrugs aciclovir and ganciclovir compared with the natural substrate. Accordingly, the mutant structure represents a first step toward improving the virus-directed enzyme-prodrug gene therapy by enzyme engineering.

Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography.,Vogt J, Perozzo R, Pautsch A, Prota A, Schelling P, Pilger B, Folkers G, Scapozza L, Schulz GE Proteins. 2000 Dec 1;41(4):545-53. PMID:11056041<ref>PMID:11056041</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1e2j" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thymidine kinase|Thymidine kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thymidine kinase]]
[[Category: Scapozza, L]]
[[Category: Schulz, G E]]
[[Category: Vogt, J]]
[[Category: Adenine analog]]
[[Category: Enzyme-prodrug gene therapy]]
[[Category: Nucleoside- binding]]
[[Category: Transferase]]