Protein Science
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print October 26, 2007, 10.1110/ps.073161707
Protein Science (2007), 16:2761-2769. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ps.073161707v1
16/12/2761    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhao, B.
Right arrow Articles by Schnackenberg, C. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, B.
Right arrow Articles by Schnackenberg, C. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

PROTEIN STRUCTURE REPORT

Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP–PNP

Baoguang Zhao1, Ruth Lehr2, Angela M. Smallwood1, Thau F. Ho2, Kathleen Maley2, Tanya Randall2, Martha S. Head1, Kristin K. Koretke1, and Christine G. Schnackenberg3

1 Department of Computational and Structural Chemistry, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA
2 Department of Biological Reagents and Assay Development, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA
3 Department of Investigative and Cardiac Biology, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA

(RECEIVED August 6, 2007; FINAL REVISION September 7, 2007; ACCEPTED September 7, 2007)

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine protein kinase of the AGC family which participates in the control of epithelial ion transport and is implicated in proliferation and apoptosis. We report here the 1.9 Å crystal structure of the catalytic domain of inactive human SGK1 in complex with AMP–PNP. SGK1 exists as a dimer formed by two intermolecular disulfide bonds between Cys258 in the activation loop and Cys193. Although most of the SGK1 structure closely resembles the common protein kinase fold, the structure around the active site is unique when compared to most protein kinases. The {alpha}C helix is not present in this inactive form of SGK1 crystal structure; instead, the segment corresponding to the C helix forms a beta-strand that is stabilized by the N-terminal segment of the activation loop through a short antiparallel beta-sheet. Since the differences from other kinases occur around the ATP binding site, this structure can provide valuable insight into the design of selective and highly potent ATP-competitive inhibitors of SGK1 kinase.

Keywords: SGK1; serine-threonine protein kinase; X-ray crystallography; crystal structure


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by The Protein Society.