1zm7: Difference between revisions
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<StructureSection load='1zm7' size='340' side='right'caption='[[1zm7]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='1zm7' size='340' side='right'caption='[[1zm7]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1zm7]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1zm7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZM7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZM7 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zm7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zm7 OCA], [https://pdbe.org/1zm7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zm7 RCSB], [https://www.ebi.ac.uk/pdbsum/1zm7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zm7 ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DNK_DROME DNK_DROME] Deoxyribonucleoside kinase that has a broad specificity phosphorylating thymidine, deoxyadenosine, deoxycytidine and deoxyguanosine. Specificity is higher for pyrimidine nucleosides. Several anti-viral and anti-cancer nucleoside analogs are also efficiently phosphorylated.<ref>PMID:10446143</ref> <ref>PMID:10692477</ref> <ref>PMID:16008571</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</div> | </div> | ||
<div class="pdbe-citations 1zm7" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1zm7" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Drosophila melanogaster]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Berenstein | [[Category: Berenstein D]] | ||
[[Category: Eklund | [[Category: Eklund H]] | ||
[[Category: Knecht | [[Category: Knecht W]] | ||
[[Category: Munch-Petersen | [[Category: Munch-Petersen B]] | ||
[[Category: Piskur | [[Category: Piskur J]] | ||
[[Category: Skovgaard | [[Category: Skovgaard T]] | ||
[[Category: Welin | [[Category: Welin M]] | ||
Latest revision as of 10:11, 23 August 2023
Crystal structure of D. melanogaster deoxyribonucleoside kinase mutant N64D in complex with dTTPCrystal structure of D. melanogaster deoxyribonucleoside kinase mutant N64D in complex with dTTP
Structural highlights
FunctionDNK_DROME Deoxyribonucleoside kinase that has a broad specificity phosphorylating thymidine, deoxyadenosine, deoxycytidine and deoxyguanosine. Specificity is higher for pyrimidine nucleosides. Several anti-viral and anti-cancer nucleoside analogs are also efficiently phosphorylated.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK) double mutant N45D/N64D was identified during a previous directed evolution study. This mutant enzyme had a decreased activity towards the natural substrates and decreased feedback inhibition with dTTP, whereas the activity with 3'-modified nucleoside analogs like 3'-azidothymidine (AZT) was nearly unchanged. Here, we identify the mutation N64D as being responsible for these changes. Furthermore, we crystallized the mutant enzyme in the presence of one of its substrates, thymidine, and the feedback inhibitor, dTTP. The introduction of the charged Asp residue appears to destabilize the LID region (residues 167-176) of the enzyme by electrostatic repulsion and no hydrogen bond to the 3'-OH is made in the substrate complex by Glu172 of the LID region. This provides a binding space for more bulky 3'-substituents like the azido group in AZT but influences negatively the interactions between Dm-dNK, substrates and feedback inhibitors based on deoxyribose. The detailed picture of the structure-function relationship provides an improved background for future development of novel mutant suicide genes for Dm-dNK-mediated gene therapy. Structural basis for the changed substrate specificity of Drosophila melanogaster deoxyribonucleoside kinase mutant N64D.,Welin M, Skovgaard T, Knecht W, Zhu C, Berenstein D, Munch-Petersen B, Piskur J, Eklund H FEBS J. 2005 Jul;272(14):3733-42. PMID:16008571[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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