|
|
| Line 1: |
Line 1: |
|
| |
|
| ==LIGAND-FREE HOMODIMERIC HUMAN GLUTATHIONE S-TRANSFERASE M4-4== | | ==LIGAND-FREE HOMODIMERIC HUMAN GLUTATHIONE S-TRANSFERASE M4-4== |
| <StructureSection load='4gtu' size='340' side='right' caption='[[4gtu]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='4gtu' size='340' side='right'caption='[[4gtu]], [[Resolution|resolution]] 3.30Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4gtu]] is a 8 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=4GTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GTU FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4gtu]] is a 8 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=4GTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GTU FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gtu|1gtu]], [[2gtu|2gtu]], [[3gtu|3gtu]]</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]] 3.3Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSTM4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4gtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gtu OCA], [https://pdbe.org/4gtu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gtu RCSB], [https://www.ebi.ac.uk/pdbsum/4gtu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gtu ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gtu OCA], [http://pdbe.org/4gtu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gtu RCSB], [http://www.ebi.ac.uk/pdbsum/4gtu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gtu ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/GSTM4_HUMAN GSTM4_HUMAN]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Active on 1-chloro-2,4-dinitrobenzene. | | [https://www.uniprot.org/uniprot/GSTM4_HUMAN GSTM4_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Active on 1-chloro-2,4-dinitrobenzene. |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 21: |
Line 19: |
| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4gtu ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4gtu ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
| |
| == 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<ref>PMID:10587441</ref>
| |
|
| |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 4gtu" style="background-color:#fffaf0;"></div>
| |
|
| |
|
| ==See Also== | | ==See Also== |
| *[[Glutathione S-transferase|Glutathione S-transferase]] | | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] |
| == 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]]
| |
| [[Category: Cytosolic]]
| |
| [[Category: Detoxification]]
| |
| [[Category: Glutathione]]
| |
| [[Category: Homodimer]]
| |
| [[Category: Transferase]]
| |
