View source for 1lbk


==Crystal structure of a recombinant glutathione transferase, created by replacing the last seven residues of each subunit of the human class pi isoenzyme with the additional C-terminal helix of human class alpha isoenzyme==
<StructureSection load='1lbk' size='340' side='right'caption='[[1lbk]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lbk]] is a 2 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=1LBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LBK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1lbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lbk OCA], [https://pdbe.org/1lbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lbk RCSB], [https://www.ebi.ac.uk/pdbsum/1lbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lbk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GSTP1_HUMAN GSTP1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.<ref>PMID:21668448</ref> 
== 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/lb/1lbk_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=1lbk ConSurf].
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== Publication Abstract from PubMed ==
We have sought the structural basis for the differing substrate specificities of human glutathione transferase P1-1 (class Pi) and human glutathione transferase A1-1 (class Alpha) by adding an extra helix (helix 9), found in the electrophilic substrate-binding site (H-site) of the human class Alpha enzyme, at the C terminus of the human class Pi enzyme. This class Pi-chimera (CODA) was expressed in Escherichia coli, purified and characterized by kinetic and crystallographic approaches. The presence of the newly engineered tail in the H-site of the human Pi enzyme alters its catalytic properties towards those exhibited by the human Alpha enzyme, as assessed using cumene hydroperoxide (diagnostic for class Alpha enzymes) and ethacrynic acid (diagnostic for class Pi) as co-substrates. There is a change of substrate selectivity in the latter case, as the k(cat)/K(m)(EA) value decreases about 70-fold, compared to that of class Pi. With 1-chloro-2,4-dinitrobenzene as co-substrate there is a loss of catalytic activity to about 2% with respect to that of the Pi enzyme. Crystallographic and kinetic studies of the class Pi-chimera provide important clues to explain these altered catalytic properties. The new helix forms many complimentary interactions with the rest of the protein and re-models the original electrophilic substrate-binding site towards one that is more enclosed, albeit flexible. Of particular note are the interactions between Glu205 of the new tail and the catalytic residues, Tyr7 and Tyr108, and the thiol moiety of glutathione (GSH). These interactions may provide an explanation of the more than one unit increase in the pK(a) value of the GSH thiolate and affect both the turnover number and GSH binding, using 1-chloro-2,4-dinitrobenzene as co-substrate. The data presented are consistent with the engineered tail adopting a highly mobile or disordered state in the apo form of the enzyme.

Engineering a new C-terminal tail in the H-site of human glutathione transferase P1-1: structural and functional consequences.,Micaloni C, Kong GK, Mazzetti AP, Nuccetelli M, Antonini G, Stella L, McKinstry WJ, Polekhina G, Rossjohn J, Federici G, Ricci G, Parker MW, Lo Bello M J Mol Biol. 2003 Jan 3;325(1):111-22. PMID:12473455<ref>PMID:12473455</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1lbk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Antonini G]]
[[Category: Federici G]]
[[Category: Kong GKW]]
[[Category: Lo Bello M]]
[[Category: Mazzetti AP]]
[[Category: McKinstry WJ]]
[[Category: Micaloni C]]
[[Category: Nuccetelli M]]
[[Category: Parker MW]]
[[Category: Polekhina G]]
[[Category: Ricci G]]
[[Category: Rossjohn J]]
[[Category: Stella L]]