2rii: Difference between revisions

Revision as of 19:47, 21 February 2008

Crystal Structure of Human Peroxiredoxin I in complex with Sulfiredoxin

OverviewOverview

Typical 2-Cys peroxiredoxins (Prxs) have an important role in regulating hydrogen peroxide-mediated cell signalling. In this process, Prxs can become inactivated through the hyperoxidation of an active site Cys residue to Cys sulphinic acid. The unique repair of this moiety by sulphiredoxin (Srx) restores peroxidase activity and terminates the signal. The hyperoxidized form of Prx exists as a stable decameric structure with each active site buried. Therefore, it is unclear how Srx can access the sulphinic acid moiety. Here we present the 2.6 A crystal structure of the human Srx-PrxI complex. This complex reveals the complete unfolding of the carboxy terminus of Prx, and its unexpected packing onto the backside of Srx away from the Srx active site. Binding studies and activity analyses of site-directed mutants at this interface show that the interaction is required for repair to occur. Moreover, rearrangements in the Prx active site lead to a juxtaposition of the Prx Gly-Gly-Leu-Gly and Srx ATP-binding motifs, providing a structural basis for the first step of the catalytic mechanism. The results also suggest that the observed interactions may represent a common mode for other proteins to bind to Prxs.

About this StructureAbout this Structure

2RII is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Peroxiredoxin, with EC number 1.11.1.15 Full crystallographic information is available from OCA.

ReferenceReference

Structure of the sulphiredoxin-peroxiredoxin complex reveals an essential repair embrace., Jonsson TJ, Johnson LC, Lowther WT, Nature. 2008 Jan 3;451(7174):98-101. PMID:18172504

Page seeded by OCA on Thu Feb 21 18:47:37 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-Typical 2-Cys peroxiredoxins (Prxs) have an important role in regulating, hydrogen peroxide-mediated cell signalling. In this process, Prxs can, become inactivated through the hyperoxidation of an active site Cys, residue to Cys sulphinic acid. The unique repair of this moiety by, sulphiredoxin (Srx) restores peroxidase activity and terminates the, signal. The hyperoxidized form of Prx exists as a stable decameric, structure with each active site buried. Therefore, it is unclear how Srx, can access the sulphinic acid moiety. Here we present the 2.6 A crystal, structure of the human Srx-PrxI complex. This complex reveals the complete, unfolding of the carboxy terminus of Prx, and its unexpected packing onto, the backside of Srx away from the Srx active site. Binding studies and, activity analyses of site-directed mutants at this interface show that the, interaction is required for repair to occur. Moreover, rearrangements in, the Prx active site lead to a juxtaposition of the Prx Gly-Gly-Leu-Gly and, Srx ATP-binding motifs, providing a structural basis for the first step of, the catalytic mechanism. The results also suggest that the observed, interactions may represent a common mode for other proteins to bind to, Prxs.
+Typical 2-Cys peroxiredoxins (Prxs) have an important role in regulating hydrogen peroxide-mediated cell signalling. In this process, Prxs can become inactivated through the hyperoxidation of an active site Cys residue to Cys sulphinic acid. The unique repair of this moiety by sulphiredoxin (Srx) restores peroxidase activity and terminates the signal. The hyperoxidized form of Prx exists as a stable decameric structure with each active site buried. Therefore, it is unclear how Srx can access the sulphinic acid moiety. Here we present the 2.6 A crystal structure of the human Srx-PrxI complex. This complex reveals the complete unfolding of the carboxy terminus of Prx, and its unexpected packing onto the backside of Srx away from the Srx active site. Binding studies and activity analyses of site-directed mutants at this interface show that the interaction is required for repair to occur. Moreover, rearrangements in the Prx active site lead to a juxtaposition of the Prx Gly-Gly-Leu-Gly and Srx ATP-binding motifs, providing a structural basis for the first step of the catalytic mechanism. The results also suggest that the observed interactions may represent a common mode for other proteins to bind to Prxs.
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Peroxiredoxin]]
 [[Category: Protein complex]]
-[[Category: Johnson, L.C.]]
+[[Category: Johnson, L C.]]
-[[Category: Jonsson, T.J.]]
+[[Category: Jonsson, T J.]]
-[[Category: Lowther, W.T.]]
+[[Category: Lowther, W T.]]
 [[Category: PO4]]
 [[Category: ----]]
@@ Line 34: / Line 34: @@
 [[Category: sulfinic acid reductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:03:57 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:47:37 2008''