English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  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. (2007). Nonenantioselectivity property of human deoxycytidine kinase explained by structures of the enzyme in complex with L- and D-Nucleosides. Journal of Medicinal Chemistry, 50(13), 3004-3014. doi:10.1021/jm0700215.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-E0DC-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-CD17-E
Genre: Journal Article

Files

show Files
hide Files
:
319653.pdf (Publisher version), 0B
 
File Permalink:
-
Name:
319653.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), Göttingen; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
595671_Suppl_1.pdf (Supplementary material), 27KB
Name:
595671_Suppl_1.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Locator:
http://pubs.acs.org/doi/full/10.1021/jm0700215 (Publisher version)
Description:
-

Creators

show
hide
 Creators:
Sabini, E., Author
Hazra, S., Author
Konrad, M.1, Author              
Lavie, A., Author
Affiliations:
1Research Group of Enzyme Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578612              

Content

show
hide
Free keywords: -
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2007-05-272007-06-28
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1021/jm0700215
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Medicinal Chemistry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 50 (13) Sequence Number: - Start / End Page: 3004 - 3014 Identifier: -