JBC Biosymposia, Inc.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on May 23, 2003
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
278/22/19933    most recent
M213006200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tabernero, L.
Right arrow Articles by Stauffacher, C. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tabernero, L.
Right arrow Articles by Stauffacher, C. V.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print March 5, 2003
J. Biol. Chem, 10.1074/jbc.M213006200
Submitted on December 20, 2002
Revised on March 5, 2003
Accepted on March 5, 2003

Crystal Structure of a Statin Bound to a Class II HMG-CoA Reductase

Lydia Tabernero, Victor W. Rodwell, and Cynthia V. Stauffacher

School of Biological Sciences, University of Manchester, Manchester M13 9PT

Corresponding Author: Lydia.Tabernero{at}man.ac.uk

HMG-CoA reductase is the primary target in the current clinical treatment of hypercholesterolemias with specific inhibitors of the "statin" family. Statins are excellent inhibitors of the class I (human) enzyme but relatively poor inhibitors of the class II enzymes of important bacterial pathogens. To investigate the molecular basis for this difference we determined the X-ray structure of the class II Pseudomonas mevalonii HMG-CoA reductase in complex with the statin drug Lovastatin. The structure shows Lovastatin bound in the active site and its interactions with residues critically involved in catalysis and substrate binding. Binding of Lovastatin also displaces the flap domain of the enzyme, which contains the catalytic residue His381. Comparison with the structures of statins bound to the human enzyme revealed a similar mode of binding, but marked differences in specific interactions that account for the observed differences in affinity. We suggest that these differences might be exploited to develop selective class II - inhibitors for use as antibacterial agents against pathogenic microorganisms.


Add to CiteULike CiteULike   Add to Complore Complore   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?


This article has been cited by other articles:


Home page
 Protein Sci.Home page
S. S. Doun, J. W. Burgner II, S. D. Briggs, and V. W. Rodwell
Enterococcus faecalis phosphomevalonate kinase
Protein Sci., May 1, 2005; 14(5): 1134 - 1139.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
M. Hedl and V. W. Rodwell
Inhibition of the Class II HMG-CoA reductase of Pseudomonas mevalonii
Protein Sci., June 1, 2004; 13(6): 1693 - 1697.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
M. Hedl, L. Tabernero, C. V. Stauffacher, and V. W. Rodwell
Class II 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductases
J. Bacteriol., April 1, 2004; 186(7): 1927 - 1932.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.