1p5z

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:05, 14 February 2024) (edit) (undo)
 
(12 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1p5z.jpg|left|200px]]
 
-
{{Structure
+
==Structure of human dCK complexed with cytarabine and ADP-MG==
-
|PDB= 1p5z |SIZE=350|CAPTION= <scene name='initialview01'>1p5z</scene>, resolution 1.60&Aring;
+
<StructureSection load='1p5z' size='340' side='right'caption='[[1p5z]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=AR3:CYTARABINE'>AR3</scene> and <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>
+
<table><tr><td colspan='2'>[[1p5z]] is a 1 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=1P5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P5Z FirstGlance]. <br>
-
|ACTIVITY= [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]
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
-
|GENE= DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+
<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=AR3:CYTARABINE'>AR3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1p5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p5z OCA], [https://pdbe.org/1p5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p5z RCSB], [https://www.ebi.ac.uk/pdbsum/1p5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p5z ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/DCK_HUMAN 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.<ref>PMID:18377927</ref> <ref>PMID:20614893</ref>
 +
== 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/p5/1p5z_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=1p5z ConSurf].
 +
<div style="clear:both"></div>
-
'''Structure of human dCK complexed with cytarabine and ADP-MG'''
+
==See Also==
-
 
+
*[[Deoxycytidine kinase 3D structures|Deoxycytidine kinase 3D structures]]
-
 
+
== References ==
-
==Overview==
+
<references/>
-
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.
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
1P5Z is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P5Z OCA].
+
-
 
+
-
==Reference==
+
-
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:[http://www.ncbi.nlm.nih.gov/pubmed/12808445 12808445]
+
-
[[Category: Deoxycytidine kinase]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Konrad, M.]]
+
[[Category: Konrad M]]
-
[[Category: Lavie, A.]]
+
[[Category: Lavie A]]
-
[[Category: Monnerjahn, C.]]
+
[[Category: Monnerjahn C]]
-
[[Category: Ort, S.]]
+
[[Category: Ort S]]
-
[[Category: Sabini, E.]]
+
[[Category: Sabini E]]
-
[[Category: ADP]]
+
-
[[Category: AR3]]
+
-
[[Category: MG]]
+
-
[[Category: arac]]
+
-
[[Category: cytarabine]]
+
-
[[Category: nucleoside kinase]]
+
-
[[Category: p-loop]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 13:10:10 2008''
+

Current revision

Structure of human dCK complexed with cytarabine and ADP-MG

PDB ID 1p5z

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1p5z"
Personal tools