2f3m: Difference between revisions
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[[Image:2f3m.gif|left|200px]] | [[Image:2f3m.gif|left|200px]] | ||
'''Structure of human GLUTATHIONE S-TRANSFERASE M1A-1A complexed with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANION''' | {{Structure | ||
|PDB= 2f3m |SIZE=350|CAPTION= <scene name='initialview01'>2f3m</scene>, resolution 2.70Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=GTD:1-(S-GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXA-2,5-DIENE'>GTD</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] | |||
|GENE= GSTM1, GST1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Structure of human GLUTATHIONE S-TRANSFERASE M1A-1A complexed with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANION''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2F3M is a [ | 2F3M is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F3M OCA]. | ||
==Reference== | ==Reference== | ||
Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a., Patskovsky Y, Patskovska L, Almo SC, Listowsky I, Biochemistry. 2006 Mar 28;45(12):3852-62. PMID:[http:// | Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a., Patskovsky Y, Patskovska L, Almo SC, Listowsky I, Biochemistry. 2006 Mar 28;45(12):3852-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16548513 16548513] | ||
[[Category: Glutathione transferase]] | [[Category: Glutathione transferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: transition state analogue]] | [[Category: transition state analogue]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:47:41 2008'' | ||
Revision as of 17:47, 20 March 2008
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| , resolution 2.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | GSTM1, GST1 (Homo sapiens) | ||||||
| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of human GLUTATHIONE S-TRANSFERASE M1A-1A complexed with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANION
OverviewOverview
An active site His107 residue distinguishes human glutathione S-transferase hGSTM1-1 from other mammalian Mu-class GSTs. The crystal structure of hGSTM1a-1a with bound glutathione (GSH) was solved to 1.9 A resolution, and site-directed mutagenesis supports the conclusion that a proton transfer occurs in which bound water at the catalytic site acts as a primary proton acceptor from the GSH thiol group to transfer the proton to His107. The structure of the second substrate-binding site (H-site) was determined from hGSTM1a-1a complexed with 1-glutathionyl-2,4-dinitrobenzene (GS-DNB) formed by a reaction in the crystal between GSH and 1-chloro-2,4-dinitrobenzene (CDNB). In that structure, the GSH-binding site (G-site) is occupied by the GSH moiety of the product in the same configuration as that of the enzyme-GSH complex, and the dinitrobenzene ring is anchored between the side chains of Tyr6, Leu12, His107, Met108, and Tyr115. This orientation suggested a distinct transition state that was substantiated from the structure of hGSTM1a-1a complexed with transition state analogue 1-S-(glutathionyl)-2,4,6-trinitrocyclohexadienate (Meisenheimer complex). Kinetic data for GSTM1a-1a indicate that kcat(CDNB) for the reaction is more than 3 times greater than kcat(FDNB), even though the nonenzymatic second-order rate constant is more than 50-fold greater for 1-fluoro-2,4-dinitrobenzene (FDNB), and the product is the same for both substrates. In addition, Km(FDNB) is about 20 times less than Km(CDNB). The results are consistent with a mechanism in which the formation of the transition state is rate-limiting in the nucleophilic aromatic substitution reactions. Data obtained with active-site mutants support transition states in which Tyr115, Tyr6, and His107 side chains are involved in the stabilization of the Meisenheimer complex via interactions with the ortho nitro group of CDNB or FDNB and provide insight into the means by which GSTs adapt to accommodate different substrates.
About this StructureAbout this Structure
2F3M is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a., Patskovsky Y, Patskovska L, Almo SC, Listowsky I, Biochemistry. 2006 Mar 28;45(12):3852-62. PMID:16548513
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