2no6

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[[Image:2no6.jpg|left|200px]]<br /><applet load="2no6" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2no6.jpg|left|200px]]
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caption="2no6, resolution 1.90&Aring;" />
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'''C4S dCK variant of dCK in complex with FTC+ADP'''<br />
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{{Structure
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|PDB= 2no6 |SIZE=350|CAPTION= <scene name='initialview01'>2no6</scene>, resolution 1.90&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> and <scene name='pdbligand=ETV:4-AMINO-5-FLUORO-1-[(2R,5S)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]PYRIMIDIN-2(1H)-ONE'>ETV</scene>
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|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]
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|GENE= DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''C4S dCK variant of dCK in complex with FTC+ADP'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2NO6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=ETV:'>ETV</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NO6 OCA].
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2NO6 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=2NO6 OCA].
==Reference==
==Reference==
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Nonenantioselectivity Property of Human Deoxycytidine Kinase Explained by Structures of the Enzyme in Complex with l- and d-Nucleosides., Sabini E, Hazra S, Konrad M, Lavie A, J Med Chem. 2007 Jun 28;50(13):3004-14. Epub 2007 May 27. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17530837 17530837]
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Nonenantioselectivity Property of Human Deoxycytidine Kinase Explained by Structures of the Enzyme in Complex with l- and d-Nucleosides., Sabini E, Hazra S, Konrad M, Lavie A, J Med Chem. 2007 Jun 28;50(13):3004-14. Epub 2007 May 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17530837 17530837]
[[Category: Deoxycytidine kinase]]
[[Category: Deoxycytidine kinase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: human deoxycytidine kinase]]
[[Category: human deoxycytidine kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:08:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:48:51 2008''

Revision as of 15:48, 20 March 2008

Image:2no6.jpg


PDB ID 2no6

Drag the structure with the mouse to rotate
, resolution 1.90Å
Ligands: and
Gene: DCK (Homo sapiens)
Activity: Deoxycytidine kinase, with EC number 2.7.1.74
Coordinates: save as pdb, mmCIF, xml



C4S dCK variant of dCK in complex with FTC+ADP


Overview

Biological molecules are predominantly enantioselective. Yet currently two nucleoside analogue prodrugs (3TC and FTC) with opposite chirality compared to physiological nucleosides are clinically approved for the treatment of HIV infections. These prodrugs require conversion to their triphosphorylated forms to achieve pharmacological activity. The first step in the activation of these agents is catalyzed by human deoxycytidine kinase (dCK). This enzyme possesses the ability to phosphorylate nucleosides of the unnatural l-chirality. To understand the molecular basis for the nonenantioselectivity of dCK, we solved the crystal structures of the enzyme in complex with the l-enantiomer and of its physiological substrate deoxycytidine and with the l-nucleoside analogue FTC. These were compared to a structure solved with d-dC. Our results highlight structural adjustments imposed on the l-nucleosides and properties of the enzyme endowing it with the ability to phosphorylate substrates with nonphysiological chirality. This work reveals the molecular basis for the activation of l-nucleosides by dCK.

About this Structure

2NO6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Nonenantioselectivity Property of Human Deoxycytidine Kinase Explained by Structures of the Enzyme in Complex with l- and d-Nucleosides., Sabini E, Hazra S, Konrad M, Lavie A, J Med Chem. 2007 Jun 28;50(13):3004-14. Epub 2007 May 27. PMID:17530837

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