1p62

From Proteopedia

(Difference between revisions)

Revision as of 07:23, 9 December 2020

Structure of human dCK complexed with gemcitabine and ADP-MG

Structural highlights

1p62 is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1p5z, 1p60, 1p61
Gene:	DCK (LK3 transgenic mice)
Activity:	Deoxycytidine kinase, with EC number 2.7.1.74
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

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

Human deoxycytidine kinase (dCK) phosphorylates the natural deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA) and is an essential enzyme for the phosphorylation of numerous nucleoside analog prodrugs routinely used in cancer and antiviral chemotherapy. For many of these compounds, the phosphorylation step catalyzed by dCK is the rate-limiting step in their overall activation pathway. To determine the factors that limit the phosphorylation efficiency of the prodrug, we solved the crystal structure of dCK to a resolution of 1.6 A in complex with its physiological substrate deoxycytidine and with the prodrugs AraC and gemcitabine. The structures reveal the determinants of dCK substrate specificity. Especially relevant to new prodrug development is the interaction between Arg128 and the hydrogen-bond acceptor at the sugar 2'-arabinosyl position of AraC and gemcitabine. On the basis of the structures, we designed a catalytically superior dCK variant that could be used in suicide gene-therapy applications.

Structure of human dCK suggests strategies to improve anticancer and antiviral therapy.,Sabini E, Ort S, Monnerjahn C, Konrad M, Lavie A Nat Struct Biol. 2003 Jul;10(7):513-9. PMID:12808445^[3]

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

References

↑ Sabini E, Hazra S, Ort S, Konrad M, Lavie A. Structural basis for substrate promiscuity of dCK. J Mol Biol. 2008 May 2;378(3):607-21. Epub 2008 Mar 3. PMID:18377927 doi:http://dx.doi.org/10.1016/j.jmb.2008.02.061
↑ Hazra S, Ort S, Konrad M, Lavie A. Structural and kinetic characterization of human deoxycytidine kinase variants able to phosphorylate 5-substituted deoxycytidine and thymidine analogues . Biochemistry. 2010 Aug 10;49(31):6784-90. PMID:20614893 doi:10.1021/bi100839e
↑ Sabini E, Ort S, Monnerjahn C, Konrad M, Lavie A. Structure of human dCK suggests strategies to improve anticancer and antiviral therapy. Nat Struct Biol. 2003 Jul;10(7):513-9. PMID:12808445 doi:http://dx.doi.org/10.1038/nsb942

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1p62"

@@ Line 1: / Line 1: @@
 ==Structure of human dCK complexed with gemcitabine and ADP-MG==
-<StructureSection load='1p62' size='340' side='right' caption='[[1p62]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='1p62' size='340' side='right'caption='[[1p62]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1p62]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P62 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P62 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1p62]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P62 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1P62 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GEO:GEMCITABINE'>GEO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GEO:GEMCITABINE'>GEO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1p5z|1p5z]], [[1p60|1p60]], [[1p61|1p61]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1p5z|1p5z]], [[1p60|1p60]], [[1p61|1p61]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </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=1p62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p62 OCA], [http://pdbe.org/1p62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p62 RCSB], [http://www.ebi.ac.uk/pdbsum/1p62 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p62 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1p62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p62 OCA], [http://pdbe.org/1p62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p62 RCSB], [http://www.ebi.ac.uk/pdbsum/1p62 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p62 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 1p62" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]]
 == References ==
 <references/>
@@ Line 36: / Line 39: @@
 </StructureSection>
 [[Category: Deoxycytidine kinase]]
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Konrad, M]]

1p62

From Proteopedia

Revision as of 07:23, 9 December 2020

Structure of human dCK complexed with gemcitabine and ADP-MG

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox