View source for 2hgs


==HUMAN GLUTATHIONE SYNTHETASE==
<StructureSection load='2hgs' size='340' side='right'caption='[[2hgs]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hgs]] is a 1 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=2HGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HGS 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]] 2.1&#8491;</td></tr>
<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=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2hgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hgs OCA], [https://pdbe.org/2hgs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hgs RCSB], [https://www.ebi.ac.uk/pdbsum/2hgs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hgs ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GSHB_HUMAN GSHB_HUMAN] Defects in GSS are the cause of glutathione synthetase deficiency (GSS deficiency) [MIM:[https://omim.org/entry/266130 266130]; also known as 5-oxoprolinuria or pyroglutamic aciduria. It is a severe form characterized by an increased rate of hemolysis and defective function of the central nervous system.  Defects in GSS are the cause of glutathione synthetase deficiency of erythrocytes (GLUSYNDE)[MIM:[https://omim.org/entry/231900 231900]. Glutathione synthetase deficiency of erythrocytes is a mild form causing hemolytic anemia.
== Function ==
[https://www.uniprot.org/uniprot/GSHB_HUMAN GSHB_HUMAN] 
== 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/hg/2hgs_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=2hgs ConSurf].
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== Publication Abstract from PubMed ==
Glutathione synthetase (GS) catalyses the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. Malfunctioning of GS results in disorders including metabolic acidosis, 5-oxoprolinuria, neurological dysfunction, haemolytic anaemia and in some cases is probably lethal. Here we report the crystal structure of human GS (hGS) at 2.1 A resolution in complex with ADP, two magnesium ions, a sulfate ion and glutathione. The structure indicates that hGS belongs to the recently identified ATP-grasp superfamily, although it displays no detectable sequence identity with other family members including its bacterial counterpart, Escherichia coli GS. The difficulty in identifying hGS as a member of the family is due in part to a rare gene permutation which has resulted in a circular shift of the conserved secondary structure elements in hGS with respect to the other known ATP-grasp proteins. Nevertheless, it appears likely that the enzyme shares the same general catalytic mechanism as other ligases. The possibility of cyclic permutations provides an insight into the evolution of this family and will probably lead to the identification of new members. Mutations that lead to GS deficiency have been mapped onto the structure, providing a molecular basis for understanding their effects.

Molecular basis of glutathione synthetase deficiency and a rare gene permutation event.,Polekhina G, Board PG, Gali RR, Rossjohn J, Parker MW EMBO J. 1999 Jun 15;18(12):3204-13. PMID:10369661<ref>PMID:10369661</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 2hgs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione synthetase|Glutathione synthetase]]
*[[TolB|TolB]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Board P]]
[[Category: Parker MW]]
[[Category: Polekhina G]]
[[Category: Rossjohn J]]