2no7

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{{STRUCTURE_2no7| PDB=2no7 | SCENE= }}
{{STRUCTURE_2no7| PDB=2no7 | SCENE= }}
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'''C4S dCK variant of dCK in complex with L-dC+ADP'''
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===C4S dCK variant of dCK in complex with L-dC+ADP===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_17530837}}
==About this Structure==
==About this Structure==
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[[Category: Human deoxycytidine kinase]]
[[Category: Human deoxycytidine kinase]]
[[Category: L-dc]]
[[Category: L-dc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:41:51 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 15:55:46 2008''

Revision as of 12:55, 27 July 2008

Image:2no7.png

Template:STRUCTURE 2no7

C4S dCK variant of dCK in complex with L-dC+ADP

Template:ABSTRACT PUBMED 17530837

About this Structure

2NO7 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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