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1ki6

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[[Image:1ki6.gif|left|200px]]<br /><applet load="1ki6" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ki6, resolution 2.37&Aring;" />
 
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'''CRYSTAL STRUCTURE OF THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE I COMPLEXED WITH A 5-IODOURACIL ANHYDROHEXITOL NUCLEOSIDE'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE I COMPLEXED WITH A 5-IODOURACIL ANHYDROHEXITOL NUCLEOSIDE==
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Antiherpes therapies are principally targeted at viral thymidine kinases and utilize nucleoside analogs, the triphosphates of which are inhibitors of viral DNA polymerase or result in toxic effects when incorporated into DNA. The most frequently used drug, aciclovir (Zovirax), is a relatively poor substrate for thymidine kinase and high-resolution structural information on drugs and other molecules binding to the target is therefore important for the design of novel and more potent chemotherapy, both in antiherpes treatment and in gene therapy systems where thymidine kinase is expressed. Here, we report for the first time the binary complexes of HSV-1 thymidine kinase (TK) with the drug molecules aciclovir and penciclovir, determined by X-ray crystallography at 2.37 A resolution. Moreover, from new data at 2.14 A resolution, the refined structure of the complex of TK with its substrate deoxythymidine (R = 0.209 for 96% of all data) now reveals much detail concerning substrate and solvent interactions with the enzyme. Structures of the complexes of TK with four halogen-containing substrate analogs have also been solved, to resolutions better than 2.4 A. The various TK inhibitors broadly fall into three groups which together probe the space of the enzyme active site in a manner that no one molecule does alone, so giving a composite picture of active site interactions that can be exploited in the design of novel compounds.
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<StructureSection load='1ki6' size='340' side='right'caption='[[1ki6]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ki6]] 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=1KI6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KI6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.37&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AHU:1,5-ANHYDRO-2,3-DIDEOXY-2-(5-IODOURACIL-1-YL)-D-ABABINO-HEXITOL'>AHU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ki6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ki6 OCA], [https://pdbe.org/1ki6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ki6 RCSB], [https://www.ebi.ac.uk/pdbsum/1ki6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ki6 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/1ki6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1ki6 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1KI6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=AHU:'>AHU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KI6 OCA].
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*[[Thymidine kinase 3D structures|Thymidine kinase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands., Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR, Proteins. 1998 Aug 15;32(3):350-61. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9715911 9715911]
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[[Category: Human alphaherpesvirus 1 strain 17]]
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[[Category: Human herpesvirus 4]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Bennett MS]]
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[[Category: Thymidine kinase]]
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[[Category: Champness JN]]
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[[Category: Bennett, M S.]]
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[[Category: Herdewijn P]]
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[[Category: Champness, J N.]]
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[[Category: Ostrowski T]]
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[[Category: Herdewijn, P.]]
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[[Category: Sanderson MR]]
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[[Category: Ostrowski, T.]]
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[[Category: Summers WC]]
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[[Category: Sanderson, M R.]]
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[[Category: Wien F]]
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[[Category: Summers, W C.]]
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[[Category: Wien, F.]]
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[[Category: AHU]]
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[[Category: SO4]]
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[[Category: 5-iodouracil anhydrohexitol nucleoside]]
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[[Category: alphaherpesvirinae]]
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[[Category: ds-dna enveloped viruses]]
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[[Category: herpesviridae]]
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[[Category: phosphotransferase]]
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[[Category: substrate analog]]
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[[Category: thymidine kinase]]
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[[Category: viridae]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:34:25 2008''
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Current revision

CRYSTAL STRUCTURE OF THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE I COMPLEXED WITH A 5-IODOURACIL ANHYDROHEXITOL NUCLEOSIDE

PDB ID 1ki6

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