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| - | [[Image:1gtu.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1gtu| PDB=1gtu | SCENE= }} | | {{STRUCTURE_1gtu| PDB=1gtu | SCENE= }} |
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| - | '''LIGAND-FREE HUMAN GLUTATHIONE S-TRANSFERASE M1A-1A'''
| + | ===LIGAND-FREE HUMAN GLUTATHIONE S-TRANSFERASE M1A-1A=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9930979}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9930979 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9930979}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Glutathione]] | | [[Category: Glutathione]] |
| | [[Category: Transferase]] | | [[Category: Transferase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:00:07 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:04:27 2008'' |
Revision as of 03:04, 1 July 2008
Template:STRUCTURE 1gtu
LIGAND-FREE HUMAN GLUTATHIONE S-TRANSFERASE M1A-1A
Template:ABSTRACT PUBMED 9930979
About this Structure
1GTU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:9930979
Page seeded by OCA on Tue Jul 1 06:04:27 2008
