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4o1l

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==Human Adenosine Kinase in complex with inhibitor==
==Human Adenosine Kinase in complex with inhibitor==
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<StructureSection load='4o1l' size='340' side='right' caption='[[4o1l]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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<StructureSection load='4o1l' size='340' side='right'caption='[[4o1l]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4o1l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O1L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O1L FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4o1l]] is a 2 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=4O1L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O1L FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HO4:5-ETHYNYL-7-(BETA-D-RIBOFURANOSYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>HO4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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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]] 2.5&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pvv|4pvv]]</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=HO4:5-ETHYNYL-7-(BETA-D-RIBOFURANOSYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>HO4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosine_kinase Adenosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.20 2.7.1.20] </span></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=4o1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1l OCA], [https://pdbe.org/4o1l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o1l RCSB], [https://www.ebi.ac.uk/pdbsum/4o1l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o1l ProSAT]</span></td></tr>
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<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=4o1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1l OCA], [http://pdbe.org/4o1l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o1l RCSB], [http://www.ebi.ac.uk/pdbsum/4o1l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o1l ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/ADK_HUMAN ADK_HUMAN]] Defects in ADK are the cause of hypermethioninemia due to adenosine kinase deficiency (HMAKD) [MIM:[http://omim.org/entry/614300 614300]]. A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.<ref>PMID:21963049</ref>
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[https://www.uniprot.org/uniprot/ADK_HUMAN ADK_HUMAN] Defects in ADK are the cause of hypermethioninemia due to adenosine kinase deficiency (HMAKD) [MIM:[https://omim.org/entry/614300 614300]. A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.<ref>PMID:21963049</ref>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/ADK_HUMAN ADK_HUMAN]] ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.
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[https://www.uniprot.org/uniprot/ADK_HUMAN ADK_HUMAN] ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Adenosine kinase (ADK) from Mycobacterium tuberculosis (Mtb) was selected as a target for design of antimycobacterial nucleosides. Screening of 7-(het)aryl-7-deazaadenine ribonucleosides with Mtb and human (h) ADKs and testing with wild-type and drug-resistant Mtb strains identified specific inhibitors of Mtb ADK with micromolar antimycobacterial activity and low cytotoxicity. X-ray structures of complexes of Mtb and hADKs with 7-ethynyl-7-deazaadenosine showed differences in inhibitor interactions in the adenosine binding sites. 1D (1)H STD NMR experiments revealed that these inhibitors are readily accommodated into the ATP and adenosine binding sites of Mtb ADK, whereas they bind preferentially into the adenosine site of hADK. Occupation of the Mtb ADK ATP site with inhibitors and formation of catalytically less competent semiopen conformation of MtbADK after inhibitor binding in the adenosine site explain the lack of phosphorylation of 7-substituted-7-deazaadenosines. Semiempirical quantum mechanical analysis confirmed different affinity of nucleosides for the Mtb ADK adenosine and ATP sites.
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Structural Basis for Inhibition of Mycobacterial and Human Adenosine Kinase by 7-Substituted 7-(Het)aryl-7-deazaadenine Ribonucleosides.,Snasel J, Naus P, Dostal J, Hnizda A, Fanfrlik J, Brynda J, Bourderioux A, Dusek M, Dvorakova H, Stolarikova J, Zabranska H, Pohl R, Konecny P, Dzubak P, Votruba I, Hajduch M, Rezacova P, Veverka V, Hocek M, Pichova I J Med Chem. 2014 Oct 23;57(20):8268-79. doi: 10.1021/jm500497v. Epub 2014 Oct 8. PMID:25259627<ref>PMID:25259627</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 4o1l" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Adenosine kinase|Adenosine kinase]]
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*[[Adenosine kinase 3D structures|Adenosine kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Adenosine kinase]]
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[[Category: Homo sapiens]]
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[[Category: Brynda, J]]
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[[Category: Large Structures]]
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[[Category: Dostal, J]]
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[[Category: Brynda J]]
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[[Category: Hodcek, M]]
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[[Category: Dostal J]]
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[[Category: Pichova, I]]
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[[Category: Hodcek M]]
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[[Category: Transferase-transferase inhibitor complex]]
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[[Category: Pichova I]]

Current revision

Human Adenosine Kinase in complex with inhibitor

PDB ID 4o1l

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