3mjr

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{{Seed}}
 
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[[Image:3mjr.png|left|200px]]
 
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==Human dCK complex with Acyclic Nucleoside==
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The line below this paragraph, containing "STRUCTURE_3mjr", creates the "Structure Box" on the page.
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<StructureSection load='3mjr' size='340' side='right'caption='[[3mjr]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3mjr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MJR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MJR FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.1&#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=AC2:9-HYROXYETHOXYMETHYLGUANINE'>AC2</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
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{{STRUCTURE_3mjr| PDB=3mjr | SCENE= }}
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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=3mjr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mjr OCA], [https://pdbe.org/3mjr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mjr RCSB], [https://www.ebi.ac.uk/pdbsum/3mjr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mjr ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DCK_HUMAN DCK_HUMAN] Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>
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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/mj/3mjr_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=3mjr ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The low toxicity of acyclovir (ACV) is mainly due to the fact that human nucleoside kinases have undetectable phosphorylation rates with this acyclic guanine analogue. In contrast, herpes virus thymidine kinase (HSV1-TK) readily activates ACV. We wanted to understand why human deoxycytidine kinase (dCK), which is related to HSV1-TK and phosphorylates deoxyguanosine, does not accept acyclic guanine analogues as substrates. Therefore, we crystallized dCK in complex with ACV at the nucleoside phosphoryl acceptor site and UDP at the phosphoryl donor site. The structure reveals that while ACV does bind at the dCK active site, it does so adopting a nonproductive conformation. Despite binding ACV, the enzyme remains in the open, inactive state. In comparison to ACV binding to HSV1-TK, in dCK, the nucleoside base adopts a different orientation related by about a 60 degrees rotation. Our analysis suggests that dCK would phosphorylate acyclic guanine analogues if they can induce a similar rotation.
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===Human dCK complex with Acyclic Nucleoside===
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The sugar ring of the nucleoside is required for productive substrate positioning in the active site of human deoxycytidine kinase (dCK): implications for the development of dCK-activated acyclic guanine analogues.,Hazra S, Konrad M, Lavie A J Med Chem. 2010 Aug 12;53(15):5792-800. PMID:20684612<ref>PMID:20684612</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3mjr" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20684612}}, adds the Publication Abstract to the page
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*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20684612 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20684612}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3MJR is a 4 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MJR OCA].
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==Reference==
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<ref group="xtra">PMID:20684612</ref><references group="xtra"/>
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[[Category: Deoxycytidine kinase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hazra, S.]]
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[[Category: Large Structures]]
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[[Category: Lavie, A.]]
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[[Category: Hazra S]]
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[[Category: Acv]]
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[[Category: Lavie A]]
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[[Category: Dck]]
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[[Category: Gcv]]
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[[Category: Kinase]]
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[[Category: Kinase activity]]
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[[Category: Nucleoside kinase]]
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[[Category: P-loop]]
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[[Category: Transferase]]
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[[Category: Udp]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 18 11:02:50 2010''
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Current revision

Human dCK complex with Acyclic Nucleoside

PDB ID 3mjr

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