English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Post-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release.

Hazra, S., Szewczak, A., Ort, S., Konrad, M., & Lavie, A. (2011). Post-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release. Biochemistry, 50(14), 2870-2880. doi:10.1021/bi2001032.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0011-578B-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CF27-3
Genre: Journal Article

Files

show Files
hide Files
:
892631.pdf (Publisher version), 6MB
 
File Permalink:
-
Name:
892631.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:
-
:
892631-Suppl.pdf (Supplementary material), 612KB
Name:
892631-Suppl.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Hazra, S., Author
Szewczak, A.1, Author              
Ort, S.1, 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: Deoxycytidine kinase (dCK) uses either ATP or UTP as a phosphoryl donor to catalyze the phosphorylation of nucleoside acceptors. The kinetic properties of human dCK are modulated in vivo by phosphorylation of serine 74. This residue is a part of the insert region and is distant from the active site. Replacing the serine with a glutamic acid (S74E variant) can mimic phosphorylation of Ser74. To understand how phosphorylation affects the catalytic properties of dCK, we examined the S74E variant of dCK both structurally and kinetically. We observe that the presence of a glutamic acid at position 74 favors the adoption by the enzyme of the open conformation. Glu74 stabilizes the open conformation by directly interacting with the indole side chain of Trp58, a residue that is in the proximity of the base of the nucleoside substrate. The open dCK conformation is competent for the binding of nucleoside but not for phosphoryl transfer. In contrast, the closed conformation is competent for phosphoryl transfer but not for product release. Thus, dCK must make the transition between the open and closed states during the catalytic cycle. We propose a reaction scheme for dCK that incorporates the transition between the open and closed states, and this serves to rationalize the observed kinetic differences between wild-type dCK and the S74E variant.

Details

show
hide
Language(s): eng - English
 Dates: 2011-02-252011-04-12
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1021/bi2001032
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Biochemistry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 50 (14) Sequence Number: - Start / End Page: 2870 - 2880 Identifier: ISSN: 0006-2960