1s5z
From Proteopedia
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| - | [[Image:1s5z.gif|left|200px]]<br /><applet load="1s5z" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1s5z, resolution 2.Å" /> | ||
| - | '''NDP kinase in complex with adenosine phosphonoacetic acid'''<br /> | ||
| - | == | + | ==NDP kinase in complex with adenosine phosphonoacetic acid== |
| + | <StructureSection load='1s5z' size='340' side='right'caption='[[1s5z]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1s5z]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S5Z 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]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SON:ADENOSINE+PHOSPHONOACETIC+ACID'>SON</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=1s5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s5z OCA], [https://pdbe.org/1s5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s5z RCSB], [https://www.ebi.ac.uk/pdbsum/1s5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s5z ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NDKC_DICDI NDKC_DICDI] | ||
| + | == 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/s5/1s5z_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=1s5z ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
NDP kinase catalyzes the last step in the phosphorylation of nucleotides. It is also involved in the activation by cellular kinases of nucleoside analogs used in antiviral therapies. Adenosine phosphonoacetic acid, a close analog of ADP already proposed as an inhibitor of ribonucleotide reductase, was found to be a poor substrate for human NDP kinase, as well as a weak inhibitor with an equilibrium dissociation constant of 0.6 mM to be compared to 0.025 mM for ADP. The X-ray structure of a complex of adenosine phosphonoacetic acid and the NDP kinase from Dictyostelium was determined to 2.0 A resolution showing that the analog adopts a binding mode similar to ADP, but that no magnesium ion is present at the active site. As ACP may also interfere with other cellular kinases, its potential as a drug targeting NDP kinase or ribonucleotide reductase is likely to be limited due to strong side effects. The design of new molecules with a narrower specificity and a stronger affinity will benefit from the detailed knowledge of the complex ACP-NDP kinase. | NDP kinase catalyzes the last step in the phosphorylation of nucleotides. It is also involved in the activation by cellular kinases of nucleoside analogs used in antiviral therapies. Adenosine phosphonoacetic acid, a close analog of ADP already proposed as an inhibitor of ribonucleotide reductase, was found to be a poor substrate for human NDP kinase, as well as a weak inhibitor with an equilibrium dissociation constant of 0.6 mM to be compared to 0.025 mM for ADP. The X-ray structure of a complex of adenosine phosphonoacetic acid and the NDP kinase from Dictyostelium was determined to 2.0 A resolution showing that the analog adopts a binding mode similar to ADP, but that no magnesium ion is present at the active site. As ACP may also interfere with other cellular kinases, its potential as a drug targeting NDP kinase or ribonucleotide reductase is likely to be limited due to strong side effects. The design of new molecules with a narrower specificity and a stronger affinity will benefit from the detailed knowledge of the complex ACP-NDP kinase. | ||
| - | + | Adenosine phosphonoacetic acid is slowly metabolized by NDP kinase.,Chen Y, Morera S, Pasti C, Angusti A, Solaroli N, Veron M, Janin J, Manfredini S, Deville-Bonne D Med Chem. 2005 Nov;1(6):529-36. PMID:16787337<ref>PMID:16787337</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1s5z" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Dictyostelium discoideum]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Angusti A]] | ||
| + | [[Category: Chen Y]] | ||
| + | [[Category: Deville-Bonne D]] | ||
| + | [[Category: Janin J]] | ||
| + | [[Category: Manfredini S]] | ||
| + | [[Category: Morera S]] | ||
| + | [[Category: Pasti C]] | ||
| + | [[Category: Solaroli N]] | ||
| + | [[Category: Veron M]] | ||
Current revision
NDP kinase in complex with adenosine phosphonoacetic acid
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