1fpy

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(New page: 200px<br /> <applet load="1fpy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fpy, resolution 2.89&Aring;" /> '''CRYSTAL STRUCTURE O...)
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[[Image:1fpy.gif|left|200px]]<br />
 
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<applet load="1fpy" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1fpy, resolution 2.89&Aring;" />
 
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'''CRYSTAL STRUCTURE OF GLUTAMINE SYNTHETASE FROM SALMONELLA TYPHIMURIUM WITH INHIBITOR PHOSPHINOTHRICIN'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF GLUTAMINE SYNTHETASE FROM SALMONELLA TYPHIMURIUM WITH INHIBITOR PHOSPHINOTHRICIN==
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Phosphinothricin is a potent inhibitor of the enzyme glutamine synthetase, (GS). The resolution of the native structure of GS from Salmonella, typhimurium has been extended to 2.5 A resolution, and the improved model, is used to determine the structure of phosphinothricin complexed to GS by, difference Fourier methods. The structure suggests a noncovalent, dead-end, mechanism of inhibition. Phosphinothricin occupies the glutamate substrate, pocket and stabilizes the Glu327 flap in a position which blocks the, glutamate entrance to the active site, trapping the inhibitor on the, enzyme. One oxygen of the phosphinyl group of phosphinothricin appears to, be protonated, because of its proximity to the carboxylate group of, Glu327. The other phosphinyl oxygen protrudes into the negatively charged, binding pocket for the substrate ammonium, disrupting that pocket. The, distribution of charges in the glutamate binding pocket is complementary, to those of phosphinothricin. The presence of a second ammonium binding, site within the active site is confirmed by its analogue thallous ion, marking the ammonium site and its protein ligands. The inhibition of GS by, methionine sulfoximine can be explained by the same mechanism. These, models of inhibited GS further illuminate its catalytic mechanism.
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<StructureSection load='1fpy' size='340' side='right'caption='[[1fpy]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1fpy]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium Salmonella enterica subsp. enterica serovar Typhimurium]. The June 2002 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Glutamine Synthetase'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2002_6 10.2210/rcsb_pdb/mom_2002_6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FPY FirstGlance]. <br>
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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]] 2.89&#8491;</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=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PPQ:PHOSPHINOTHRICIN'>PPQ</scene></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=1fpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fpy OCA], [https://pdbe.org/1fpy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fpy RCSB], [https://www.ebi.ac.uk/pdbsum/1fpy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fpy ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GLN1B_SALTY GLN1B_SALTY] Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia.<ref>PMID:7727369</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fp/1fpy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</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/main_output.php?pdb_ID=1fpy ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1FPY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium] with MN, ADP and PPQ as [http://en.wikipedia.org/wiki/ligands ligands]. The following page contains interesting information on the relation of 1FPY with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb30_1.html Glutamine Synthetase]]. Active as [http://en.wikipedia.org/wiki/Glutamate--ammonia_ligase Glutamate--ammonia ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.1.2 6.3.1.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FPY OCA].
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*[[Glutamine synthetase 3D structures|Glutamine synthetase 3D structures]]
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== References ==
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==Reference==
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<references/>
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The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition., Gill HS, Eisenberg D, Biochemistry. 2001 Feb 20;40(7):1903-12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11329256 11329256]
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__TOC__
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[[Category: Glutamate--ammonia ligase]]
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</StructureSection>
[[Category: Glutamine Synthetase]]
[[Category: Glutamine Synthetase]]
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[[Category: Salmonella typhimurium]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Eisenberg, D.]]
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[[Category: Salmonella enterica subsp. enterica serovar Typhimurium]]
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[[Category: Gill, H.S.]]
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[[Category: Eisenberg D]]
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[[Category: ADP]]
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[[Category: Gill HS]]
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[[Category: MN]]
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[[Category: PPQ]]
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[[Category: glutamine synthetase]]
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[[Category: inhibition]]
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[[Category: phosphinothricin]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:00:23 2007''
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Current revision

CRYSTAL STRUCTURE OF GLUTAMINE SYNTHETASE FROM SALMONELLA TYPHIMURIUM WITH INHIBITOR PHOSPHINOTHRICIN

PDB ID 1fpy

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