JBC

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


     

A more recent version of this article appeared on November 2, 2001
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
276/45/42138    most recent
M102344200v1
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 Lo Bello, M.
Right arrow Articles by Ricci, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lo Bello, M.
Right arrow Articles by Ricci, G.
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 August 31, 2001
J. Biol. Chem, 10.1074/jbc.M102344200
Submitted on March 15, 2001
Revised on August 30, 2001
Accepted on August 31, 2001

Human glutathione transferase P1-1 and nitric oxide carriers: A new role for an old enzyme

Mario Lo Bello, Marzia Nuccetelli, Anna M. Caccuri, Lorenzo Stella, Michael W. Parker, Jamie Rossjohn, William J. McKinstry, Alessia F. Mozzi, Giorgio Federici, Francesca Polizio, Jens Z. Pedersen, and Giorgio Ricci

Department of Biology, University of Rome Tor Vergata, Rome 00133

Corresponding Author: lobello{at}uniroma2.it

S-Nitrosoglutathione and the dinitrosyl-diglutathionyl iron complex are involved in the storage and transport of NO in biological systems. Their interactions with the human glutathione transferase P1-1 may reveal an additional physiological role for this enzyme. In the absence of GSH, GSNO causes rapid and stable S-nitrosylation of both Cys 47 and Cys 101 residues. Ionspray ionization-mass spectrometry ruled out the possibility of S-glutathionylation and confirms the occurrence of a poly-S-nitrosylation in GST P1-1. S-nitrosylation of Cys 47 lowers the affinity tenfold for GSH, but this negative effect is minimized by half-site reactivity mechanism which protects one Cys 47 per dimer from nitrosylation. Thus, glutathione transferase P1-1, retaining most of its original activity, may act as a NO-carrier protein when GSH depletion occurs in the cell. The dinitrosyl-diglutathionyl iron complex, which is formed by GSNO decomposition in the presence of physiological concentrations of GSH and traces of ferrous ions, binds with extraordinary affinity to one active site of this dimeric enzyme (Ki < 10-12 M) and triggers negative cooperativity in the vacant subunit (Ki = 10-9 M). The complex bound to the enzyme is stable for hours while, in the free form and at low concentrations, its life time is only a few minutes. ESR and molecular modelling studies provide a reasonable explanation of this strong interaction suggesting that Tyr 7 and enzyme-bound GSH could be involved in the coordination of the iron atom. All the observed findings suggest that glutathione transferase P1-1, by means of an intersubunit communication, may act as a NO carrier under different cellular conditions, whilst maintaining its well known detoxificating activity towards dangerous compounds.


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
J. Z. Pedersen, F. De Maria, P. Turella, G. Federici, M. Mattei, R. Fabrini, K. F. Dawood, M. Massimi, A. M. Caccuri, and G. Ricci
Glutathione Transferases Sequester Toxic Dinitrosyl-Iron Complexes in Cells: A PROTECTION MECHANISM AGAINST EXCESS NITRIC OXIDE
J. Biol. Chem., March 2, 2007; 282(9): 6364 - 6371.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Stella, V. Pallottini, S. Moreno, S. Leoni, F. De Maria, P. Turella, G. Federici, R. Fabrini, K. F. Dawood, M. L. Bello, et al.
Electrostatic Association of Glutathione Transferase to the Nuclear Membrane: EVIDENCE OF AN ENZYME DEFENSE BARRIER AT THE NUCLEAR ENVELOPE
J. Biol. Chem., March 2, 2007; 282(9): 6372 - 6379.
[Abstract] [Full Text] [PDF]

Home page
 J ANIM SCIHome page
M. Hamelin, T. Sayd, C. Chambon, J. Bouix, B. Bibe, D. Milenkovic, H. Leveziel, M. Georges, A. Clop, P. Marinova, et al.
Proteomic analysis of ovine muscle hypertrophy
J Anim Sci, December 1, 2006; 84(12): 3266 - 3276.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
R. Tellez-Sanz, E. Cesareo, M. Nuccetelli, A. M. Aguilera, C. Baron, L. J. Parker, J. J. Adams, C. J. Morton, M. Lo Bello, M. W. Parker, et al.
Calorimetric and structural studies of the nitric oxide carrier S-nitrosoglutathione bound to human glutathione transferase P1-1
Protein Sci., May 1, 2006; 15(5): 1093 - 1105.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Cesareo, L. J. Parker, J. Z. Pedersen, M. Nuccetelli, A. P. Mazzetti, A. Pastore, G. Federici, A. M. Caccuri, G. Ricci, J. J. Adams, et al.
Nitrosylation of Human Glutathione Transferase P1-1 with Dinitrosyl Diglutathionyl Iron Complex in Vitro and in Vivo
J. Biol. Chem., December 23, 2005; 280(51): 42172 - 42180.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. G. Kilili, N. Atanassova, A. Vardanyan, N. Clatot, K. Al-Sabarna, P. N. Kanellopoulos, A. M. Makris, and S. C. Kampranis
Differential Roles of Tau Class Glutathione S-Transferases in Oxidative Stress
J. Biol. Chem., June 4, 2004; 279(23): 24540 - 24551.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. Liu, C. Li, W. Qu, E. Leslie, C. L. Bonifant, G. S. Buzard, J. E. Saavedra, L. K. Keefer, and M. P. Waalkes
Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation
Mol. Cancer Ther., June 1, 2004; 3(6): 709 - 714.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. D. Maria, J. Z. Pedersen, A. M. Caccuri, G. Antonini, P. Turella, L. Stella, M. L. Bello, G. Federici, and G. Ricci
The Specific Interaction of Dinitrosyl-Diglutathionyl-Iron Complex, a Natural NO Carrier, with the Glutathione Transferase Superfamily: SUGGESTION FOR AN EVOLUTIONARY PRESSURE IN THE DIRECTION OF THE STORAGE OF NITRIC OXIDE
J. Biol. Chem., October 24, 2003; 278(43): 42283 - 42293.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Turella, J. Z. Pedersen, A. M. Caccuri, F. De Maria, P. Mastroberardino, M. L. Bello, G. Federici, and G. Ricci
Glutathione Transferase Superfamily Behaves Like Storage Proteins for Dinitrosyl-Diglutathionyl-Iron Complex in Heterogeneous Systems
J. Biol. Chem., October 24, 2003; 278(43): 42294 - 42299.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.