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| - | [[Image:4gtu.gif|left|200px]] | |
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| - | {{Structure
| + | ==LIGAND-FREE HOMODIMERIC HUMAN GLUTATHIONE S-TRANSFERASE M4-4== |
| - | |PDB= 4gtu |SIZE=350|CAPTION= <scene name='initialview01'>4gtu</scene>, resolution 3.3Å
| + | <StructureSection load='4gtu' size='340' side='right'caption='[[4gtu]], [[Resolution|resolution]] 3.30Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <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> |
| - | |ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | |GENE= GSTM4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <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> |
| - | |DOMAIN=
| + | </table> |
| - | |RELATEDENTRY=[[1gtu|1GTU]], [[2gtu|2GTU]], [[3gtu|3GTU]]
| + | == Function == |
| - | |RESOURCES=<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://www.ebi.ac.uk/pdbsum/4gtu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=4gtu RCSB]</span>
| + | [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 == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gt/4gtu_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </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> |
| | | | |
| - | '''LIGAND-FREE HOMODIMERIC HUMAN GLUTATHIONE S-TRANSFERASE M4-4'''
| + | ==See Also== |
| - | | + | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | 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.
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| - | | + | |
| - | ==About this Structure==
| + | |
| - | 4GTU 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=4GTU OCA].
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| - | | + | |
| - | ==Reference==
| + | |
| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10587441 10587441]
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| - | [[Category: Glutathione transferase]]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[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: homodimer]]
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| - | [[Category: transferase]]
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:39:00 2008''
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