1gtu: Difference between revisions
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[[Image:1gtu.gif|left|200px]] | [[Image:1gtu.gif|left|200px]] | ||
'''LIGAND-FREE HUMAN GLUTATHIONE S-TRANSFERASE M1A-1A''' | {{Structure | ||
|PDB= 1gtu |SIZE=350|CAPTION= <scene name='initialview01'>1gtu</scene>, resolution 2.68Å | |||
|SITE= | |||
|LIGAND= | |||
|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= GSTM1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''LIGAND-FREE HUMAN GLUTATHIONE S-TRANSFERASE M1A-1A''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1GTU is a [ | 1GTU 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=1GTU OCA]. | ||
==Reference== | ==Reference== | ||
Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a., Patskovsky YV, Patskovska LN, Listowsky I, Biochemistry. 1999 Jan 26;38(4):1193-202. PMID:[http:// | Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a., Patskovsky YV, Patskovska LN, Listowsky I, Biochemistry. 1999 Jan 26;38(4):1193-202. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9930979 9930979] | ||
[[Category: Glutathione transferase]] | [[Category: Glutathione transferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''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 11:27:50 2008'' | ||
Revision as of 12:27, 20 March 2008
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| , resolution 2.68Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | GSTM1A (Homo sapiens) | ||||||
| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
LIGAND-FREE HUMAN GLUTATHIONE S-TRANSFERASE M1A-1A
OverviewOverview
Domain interchange analyses and site-directed mutagenesis indicate that the His107 residue of the human subunit hGSTM1 has a pronounced influence on catalysis of nucleophilic aromatic substitution reactions, and a H107S substitution accounts for the marked differences in the properties of the homologous hGSTM1-1 (His107) and hGSTM4-4 (Ser107) glutathione S-transferases. Reciprocal replacement of His107 and Ser107 in chimeric enzymes results in reciprocal conversion of catalytic properties. With 1-chloro-2, 4-dinitrobenzene as a substrate, the His107 residue primarily influences the pH dependence of catalysis by lowering the apparent pKa of kcat/Km from 7.8 for the Ser107-containing enzymes to 6.3 for the His107-containing enzymes. There is a parallel shift in the pKa for thiolate anion formation of enzyme-bound GSH. Y6F mutations have no effect on the pKa for these enzymes. Crystal structures of hGSTM1a-1a indicate that the imidazole ring of His107 is oriented toward the substrate binding cleft approximately 6 A from the GSH thiol group. Thus, His107 has the potential to act as a general base in proton transfer mediated through an active site water molecule or directly following a modest conformational change, to promote thiolate anion formation. All wild-type enzymes and H107S chimera have nearly identical equilibrium constants for formation of enzyme-GSH complexes (Kd values of 1-2 x 10(-)6 M); however, KmGSH and Ki values for S-methylglutathione inhibition determined by steady-state kinetics are nearly 100-fold higher. The functions of His107 of hGSTM1a-1a are unexpected in view of a substantial body of previous evidence that excluded participation of histidine residues in the catalytic mechanisms of other glutathione S-transferases. Consequences of His107 involvement in catalysis are also substrate-dependent; in contrast to 1-chloro-2,4-dinitrobenzene, for the nucleophilic addition reaction of GSH to ethacrynic acid, the H107S substitution has no effect on catalysis presumably because product release is rate-limiting.
About this StructureAbout this Structure
1GTU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a., Patskovsky YV, Patskovska LN, Listowsky I, Biochemistry. 1999 Jan 26;38(4):1193-202. PMID:9930979
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