JBC

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


     

A more recent version of this article appeared on December 24, 2004
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
279/52/54216    most recent
M411177200v1
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 Song, E. S.
Right arrow Articles by Hersh, L. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Song, E. S.
Right arrow Articles by Hersh, L. B.
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 October 19, 2004
J. Biol. Chem, 10.1074/jbc.M411177200
Submitted on September 29, 2004
Revised on October 19, 2004
Accepted on October 19, 2004

ATP affects on insulin degrading enzyme are mediated primarily through its triphosphate moiety

Eun Suk Song, Maria Aparecida Juliano, Luiz Juliano, Michael G. Fried, Steven L. Wagner, and Louis B. Hersh

Deaprtment of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536-0298

Corresponding Author: lhersh{at}uky.edu

It has previously been reported that ATP inhibits the insulysin (IDE) reaction (Camberos et al., Exp. Biol. Med. 226, 334-341, 2001). We report here that with Abz-GGFLRKHGQ-EDDnp as substrate, ATP and other nucleotides increase the rate >20 fold in Tris buffer. There is no specificity with respect to the nucleotide, however ATP is more effective than ADP, which is more effective than AMP. Triphosphate itself was as effective as ATP, indicating it is this moiety responsible for activation. The binding of triphosphate was shown to be at a site distinct from the active site, thus acting as a non-competitive activator. With the physiological substrates insulin and amyloid b peptide, nucleotides and triphosphate were without effect. However, with small physiological peptides such a bradykinin and dynorphin B-9, ATP and triphosphate increased the rate of hydrolysis ~10 fold. Triphosphate and ATP shifted the oligomeric state of the enzyme from primarily dimer-tetramers to a monomer. These data suggest the presence of an allosteric regulatory site on insulysin that may that shifts its specificity toward small peptide substrates.


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
 J. Biol. Chem.Home page
H. Im, M. Manolopoulou, E. Malito, Y. Shen, J. Zhao, M. Neant-Fery, C.-Y. Sun, S. C. Meredith, S. S. Sisodia, M. A. Leissring, et al.
Structure of Substrate-free Human Insulin-degrading Enzyme (IDE) and Biophysical Analysis of ATP-induced Conformational Switch of IDE
J. Biol. Chem., August 31, 2007; 282(35): 25453 - 25463.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Kim, L. B. Hersh, M. A. Leissring, M. Ingelsson, T. Matsui, W. Farris, A. Lu, B. T. Hyman, D. J. Selkoe, L. Bertram, et al.
Decreased Catalytic Activity of the Insulin-degrading Enzyme in Chromosome 10-Linked Alzheimer Disease Families
J. Biol. Chem., March 16, 2007; 282(11): 7825 - 7832.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
M. del Carmen Camberos and J. C. Cresto
Insulin-Degrading Enzyme Hydrolyzes ATP
Experimental Biology and Medicine, February 1, 2007; 232(2): 281 - 292.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. S. Song, A. Daily, M. G. Fried, M. A. Juliano, L. Juliano, and L. B. Hersh
Mutation of Active Site Residues of Insulin-degrading Enzyme Alters Allosteric Interactions
J. Biol. Chem., May 6, 2005; 280(18): 17701 - 17706.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.