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| | {{STRUCTURE_1b48| PDB=1b48 | SCENE= }} | | {{STRUCTURE_1b48| PDB=1b48 | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE OF MGSTA4-4 IN COMPLEX WITH GSH CONJUGATE OF 4-HYDROXYNONENAL IN ONE SUBUNIT AND GSH IN THE OTHER: EVIDENCE OF SIGNALING ACROSS DIMER INTERFACE IN MGSTA4-4'''
| + | ===CRYSTAL STRUCTURE OF MGSTA4-4 IN COMPLEX WITH GSH CONJUGATE OF 4-HYDROXYNONENAL IN ONE SUBUNIT AND GSH IN THE OTHER: EVIDENCE OF SIGNALING ACROSS DIMER INTERFACE IN MGSTA4-4=== |
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| - | ==Overview==
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| - | mGSTA4-4, a murine glutathione S-transferase (GST) exhibiting high activity in conjugating the lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) with glutathione (GSH), was crystallized in complex with the GSH conjugate of 4-HNE (GS-Hna). The structure has been solved at 2.6 A resolution, which reveals that the active site of one subunit of the dimeric enzyme binds GS-Hna, whereas the other binds GSH. A marked asymmetry between the two subunits is evident. Most noticeable are the differences in the conformation of arginine residues 69 and 15. In all GST structures published previously, the guanidino groups of R69 residues from both subunits stack at the dimer interface and are related by a (pseudo-) 2-fold axis. In the present structure of mGSTA4-4, however, the two R69 side chains point in opposite directions, although their guanidino groups remain in contact. In the subunit with bound GSH, R69 also interacts with R15, and the guanidino group of R15 points away from the active site, whereas in the subunit that binds GS-Hna, R15 pivots into the active site, which breaks its interaction with R69. According to our previous results [Nanduri et al. (1997) Arch. Biochem. Biophys. 335, 305-310], the availability of R15 in the active site assists the conjugation of 4-HNE with GSH. We propose a model for the catalytic mechanism of mGSTA4-4 in conjugating 4-HNE with GSH-i.e., the guanidino group of R15 is available in the active site of only one subunit at any given time and the stacked pair of R69 residues act as a switch that couples the concerted movement of the two R15 side chains. The alternate occupancy of 4-HNE in the two subunits has been confirmed by our kinetic analysis that shows the negative cooperativity of mGSTA4-4 for 4-HNE. Disruption of the signaling between the subunits by mutating the R69 residues released the negative cooperativity with 4-HNE.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10508391}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10508391 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10508391}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Gst]] | | [[Category: Gst]] |
| | [[Category: Subunit cooperativity]] | | [[Category: Subunit cooperativity]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:02:50 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 18:12:54 2008'' |
Revision as of 15:12, 30 June 2008
Template:STRUCTURE 1b48
CRYSTAL STRUCTURE OF MGSTA4-4 IN COMPLEX WITH GSH CONJUGATE OF 4-HYDROXYNONENAL IN ONE SUBUNIT AND GSH IN THE OTHER: EVIDENCE OF SIGNALING ACROSS DIMER INTERFACE IN MGSTA4-4
Template:ABSTRACT PUBMED 10508391
About this Structure
1B48 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structure of a murine glutathione S-transferase in complex with a glutathione conjugate of 4-hydroxynon-2-enal in one subunit and glutathione in the other: evidence of signaling across the dimer interface., Xiao B, Singh SP, Nanduri B, Awasthi YC, Zimniak P, Ji X, Biochemistry. 1999 Sep 14;38(37):11887-94. PMID:10508391
Page seeded by OCA on Mon Jun 30 18:12:54 2008
