2d33

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==Crystal Structure of gamma-Glutamylcysteine Synthetase Complexed with Aluminum Fluoride==
==Crystal Structure of gamma-Glutamylcysteine Synthetase Complexed with Aluminum Fluoride==
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<StructureSection load='2d33' size='340' side='right' caption='[[2d33]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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<StructureSection load='2d33' size='340' side='right'caption='[[2d33]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2d33]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D33 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2D33 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2d33]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2D33 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2d32|2d32]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gshI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2d33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d33 OCA], [https://pdbe.org/2d33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2d33 RCSB], [https://www.ebi.ac.uk/pdbsum/2d33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2d33 ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamate--cysteine_ligase Glutamate--cysteine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.2 6.3.2.2] </span></td></tr>
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<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=2d33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d33 OCA], [http://pdbe.org/2d33 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2d33 RCSB], [http://www.ebi.ac.uk/pdbsum/2d33 PDBsum]</span></td></tr>
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</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GSH1_ECOLI GSH1_ECOLI]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d3/2d33_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d3/2d33_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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</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=2d33 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Gamma-glutamylcysteine synthetase (gammaGCS), a rate-limiting enzyme in glutathione biosynthesis, plays a central role in glutathione homeostasis and is a target for development of potential therapeutic agents against parasites and cancer. We have determined the crystal structures of Escherichia coli gammaGCS unliganded and complexed with a sulfoximine-based transition-state analog inhibitor at resolutions of 2.5 and 2.1 A, respectively. In the crystal structure of the complex, the bound inhibitor is phosphorylated at the sulfoximido nitrogen and is coordinated to three Mg2+ ions. The cysteine-binding site was identified; it is formed inductively at the transition state. In the unliganded structure, an open space exists around the representative cysteine-binding site and is probably responsible for the competitive binding of glutathione. Upon inhibitor binding, the side chains of Tyr-241 and Tyr-300 turn, forming a hydrogen-bonding triad with the carboxyl group of the inhibitor's cysteine moiety, allowing this moiety to fit tightly into the cysteine-binding site with concomitant accommodation of its side chain into a shallow pocket. This movement is caused by a conformational change of a switch loop (residues 240-249). Based on this crystal structure, the cysteine-binding sites of mammalian and parasitic gammaGCSs were predicted by multiple sequence alignment, although no significant sequence identity exists between the E. coli gammaGCS and its eukaryotic homologues. The identification of this cysteine-binding site provides important information for the rational design of novel gammaGCS inhibitors.
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Escherichia coli B gamma-glutamylcysteine synthetase (gammaGCS) catalyzes the ATP-dependent coupling of L-Glu and L-Cys to form the glutathione precursor gamma-L-Glu-Cys and is a target for development of potential therapeutic agents. By introducing four point mutations of surface-exposed cysteine residues to serine, the gammaGCS was purified to homogeneity; single crystals have been obtained using the hanging-drop vapour-diffusion method with sodium formate. The gammaGCS crystal diffracted to 2.8 A and belongs to space group R3, with unit-cell parameters a = b = 326.7, c = 103.9 A.
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Crystal structure of gamma-glutamylcysteine synthetase: insights into the mechanism of catalysis by a key enzyme for glutathione homeostasis.,Hibi T, Nii H, Nakatsu T, Kimura A, Kato H, Hiratake J, Oda J Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15052-7. Epub 2004 Oct 11. PMID:15477603<ref>PMID:15477603</ref>
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Escherichia coli B gamma-glutamylcysteine synthetase: modification, purification, crystallization and preliminary crystallographic analysis.,Hibi T, Hisada H, Nakatsu T, Kato H, Oda J Acta Crystallogr D Biol Crystallogr. 2002 Feb;58(Pt 2):316-8. Epub 2002, Jan 24. PMID:011807262<ref>PMID:011807262</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillus coli migula 1895]]
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[[Category: Escherichia coli]]
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[[Category: Glutamate--cysteine ligase]]
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[[Category: Large Structures]]
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[[Category: Hibi, T]]
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[[Category: Hibi T]]
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[[Category: Katano, H]]
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[[Category: Katano H]]
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[[Category: Kurokawa, Y]]
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[[Category: Kurokawa Y]]
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[[Category: Nakayama, M]]
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[[Category: Nakayama M]]
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[[Category: Nii, H]]
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[[Category: Nii H]]
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[[Category: Oda, J]]
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[[Category: Oda J]]
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[[Category: Glutathione homeostasis]]
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[[Category: Ligase]]
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[[Category: Peptide synthesis]]
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[[Category: Phosphoryl transfer]]
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Current revision

Crystal Structure of gamma-Glutamylcysteine Synthetase Complexed with Aluminum Fluoride

PDB ID 2d33

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