2jj8

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Revision as of 11:25, 11 September 2015

Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase

Structural highlights

2jj8 is a 4 chain structure with sequence from Drome. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1zm7, 2vpp, 2vp5, 1zmx, 2vp4, 1j90, 2vp0, 2jcs, 1ot3, 2vp6, 1oe0, 2vp2, 2vp9, 2vqs
Activity:	Deoxynucleoside kinase, with EC number 2.7.1.145
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[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 PubMed

The Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (dNK; EC 2.7.1.145) has a high turnover rate and a wide substrate range that makes it a very good candidate for gene therapy. This concept is based on introducing a suicide gene into malignant cells in order to activate a prodrug that eventually may kill the cell. To be able to optimize the function of dNK, it is vital to have structural information of dNK complexes. In this study we present crystal structures of dNK complexed with four different nucleoside analogs (floxuridine, brivudine, zidovudine and zalcitabine) and relate them to the binding of substrate and feedback inhibitors. dCTP and dGTP bind with the base in the substrate site, similarly to the binding of the feedback inhibitor dTTP. All nucleoside analogs investigated bound in a manner similar to that of the pyrimidine substrates, with many interactions in common. In contrast, the base of dGTP adopted a syn-conformation to adapt to the available space of the active site.

Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase.,Mikkelsen NE, Munch-Petersen B, Eklund H FEBS J. 2008 May;275(9):2151-60. Epub 2008 Apr 1. PMID:18384378^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Johansson M, van Rompay AR, Degreve B, Balzarini J, Karlsson A. Cloning and characterization of the multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster. J Biol Chem. 1999 Aug 20;274(34):23814-9. PMID:10446143
↑ Munch-Petersen B, Knecht W, Lenz C, Sondergaard L, Piskur J. Functional expression of a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster and its C-terminal deletion mutants. J Biol Chem. 2000 Mar 3;275(9):6673-9. PMID:10692477
↑ Welin M, Skovgaard T, Knecht W, Zhu C, Berenstein D, Munch-Petersen B, Piskur J, Eklund H. Structural basis for the changed substrate specificity of Drosophila melanogaster deoxyribonucleoside kinase mutant N64D. FEBS J. 2005 Jul;272(14):3733-42. PMID:16008571 doi:10.1111/j.1742-4658.2005.04803.x
↑ Mikkelsen NE, Munch-Petersen B, Eklund H. Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase. FEBS J. 2008 May;275(9):2151-60. Epub 2008 Apr 1. PMID:18384378 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06369.x

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2jj8"

@@ Line 2: / Line 2: @@
 <StructureSection load='2jj8' size='340' side='right' caption='[[2jj8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2jj8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JJ8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2jj8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JJ8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZZ:3-AZIDO-3-DEOXYTHYMIDINE'>AZZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zm7|1zm7]], [[2vpp|2vpp]], [[2vp5|2vp5]], [[1zmx|1zmx]], [[2vp4|2vp4]], [[1j90|1j90]], [[2vp0|2vp0]], [[2jcs|2jcs]], [[1ot3|1ot3]], [[2vp6|2vp6]], [[1oe0|1oe0]], [[2vp2|2vp2]], [[2vp9|2vp9]], [[2vqs|2vqs]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxynucleoside_kinase Deoxynucleoside kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.145 2.7.1.145] </span></td></tr>
-<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=2jj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jj8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jj8 RCSB], [http://www.ebi.ac.uk/pdbsum/2jj8 PDBsum]</span></td></tr>
+<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=2jj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jj8 OCA], [http://pdbe.org/2jj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jj8 RCSB], [http://www.ebi.ac.uk/pdbsum/2jj8 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2jj8" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 33: / Line 34: @@
 </StructureSection>
 [[Category: Deoxynucleoside kinase]]
-[[Category: Drosophila melanogaster]]
+[[Category: Drome]]
 [[Category: Eklund, H]]
 [[Category: Mikkelsen, N E]]

2jj8

From Proteopedia

Revision as of 11:25, 11 September 2015

Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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