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| ==LIGAND-FREE HETERODIMERIC HUMAN GLUTATHIONE S-TRANSFERASE M2-3 (EC 2.5.1.18), MONOCLINIC CRYSTAL FORM== | | ==LIGAND-FREE HETERODIMERIC HUMAN GLUTATHIONE S-TRANSFERASE M2-3 (EC 2.5.1.18), MONOCLINIC CRYSTAL FORM== |
- | <StructureSection load='3gtu' size='340' side='right' caption='[[3gtu]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3gtu' size='340' side='right'caption='[[3gtu]], [[Resolution|resolution]] 2.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[3gtu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GTU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gtu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GTU FirstGlance]. <br> |
- | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSTM2, GSTM3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gtu OCA], [https://pdbe.org/3gtu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gtu RCSB], [https://www.ebi.ac.uk/pdbsum/3gtu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gtu ProSAT]</span></td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gtu OCA], [http://pdbe.org/3gtu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gtu RCSB], [http://www.ebi.ac.uk/pdbsum/3gtu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gtu ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/GSTM2_HUMAN GSTM2_HUMAN]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.<ref>PMID:16549767</ref> [[http://www.uniprot.org/uniprot/GSTM3_HUMAN GSTM3_HUMAN]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers.<ref>PMID:10587441</ref> | + | [https://www.uniprot.org/uniprot/GSTM2_HUMAN GSTM2_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.<ref>PMID:16549767</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| ==See Also== | | ==See Also== |
- | *[[Glutathione S-transferase|Glutathione S-transferase]] | + | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Glutathione transferase]] | + | [[Category: Homo sapiens]] |
- | [[Category: Human]] | + | [[Category: Large Structures]] |
- | [[Category: Listowsky, I]] | + | [[Category: Listowsky I]] |
- | [[Category: Patskovska, L N]] | + | [[Category: Patskovska LN]] |
- | [[Category: Patskovsky, Y V]] | + | [[Category: Patskovsky YV]] |
- | [[Category: Conjugation]]
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- | [[Category: Cytosolic]]
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- | [[Category: Detoxification]]
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- | [[Category: Glutathione]]
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- | [[Category: Heterodimer]]
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- | [[Category: Transferase]]
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| Structural highlights
Function
GSTM2_HUMAN Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The hGSTM3 subunit, which is preferentially expressed in germ-line cells, has the greatest sequence divergence among the human mu class glutathione S-transferases. To determine a structural basis for the catalytic differences between hGSTM3-3 and other mu class enzymes, chimeric proteins were designed by modular interchange of the divergent C-terminal domains of hGSTM3 and hGSTM5 subunits. Replacement of 24 residues of the C-terminal segment of either subunit produced chimeric enzymes with catalytic properties that reflected those of the wild-type enzyme from which the C-terminus had been derived. Deletion of the tripeptide C-terminal extension found only in the hGSTM3 subunit had no effect on catalysis. The crystal structure determined for a ligand-free hGSTM3 subunit indicates that an Asn212 residue of the C-terminal domain is near a hydrophobic cluster of side chains formed in part by Ile13, Leu16, Leu114, Ile115, Tyr119, Ile211, and Trp218. Accordingly, a series of point mutations were introduced into the hGSTM3 subunit, and it was indeed determined that a Y119F mutation considerably enhanced the turnover rate of the enzyme for nucleophilic aromatic substitution reactions. A more striking effect was observed for a double mutant (Y119F/N212F) which had a k(cat)/K(m)(CDNB) value of 7.6 x 10(5) s(-)(1) M(-)(1) as compared to 4.9 x 10(3) s(-)(1) M(-)(1) for the wild-type hGSTM3-3 enzyme. The presence of a polar Asn212 in place of a Phe residue found in the cognate position of other mu class glutathione S-transferases, therefore, has a marked influence on catalysis by hGSTM3-3.
An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases.,Patskovsky YV, Patskovska LN, Listowsky I Biochemistry. 1999 Dec 7;38(49):16187-94. PMID:10587441[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Norrgard MA, Ivarsson Y, Tars K, Mannervik B. Alternative mutations of a positively selected residue elicit gain or loss of functionalities in enzyme evolution. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4876-81. Epub 2006 Mar 20. PMID:16549767
- ↑ Patskovsky YV, Patskovska LN, Listowsky I. An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases. Biochemistry. 1999 Dec 7;38(49):16187-94. PMID:10587441
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