View source for 1grh


==INHIBITION OF HUMAN GLUTATHIONE REDUCTASE BY THE NITROSOUREA DRUGS 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA AND 1-(2-CHLOROETHYL)-3-(2-HYDROXYETHYL)-1-NITROSOUREA==
<StructureSection load='1grh' size='340' side='right'caption='[[1grh]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1grh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GRH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1grg|1grg]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glutathione-disulfide_reductase Glutathione-disulfide reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.7 1.8.1.7] </span></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=1grh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1grh OCA], [https://pdbe.org/1grh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1grh RCSB], [https://www.ebi.ac.uk/pdbsum/1grh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1grh ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/GSHR_HUMAN GSHR_HUMAN]] Maintains high levels of reduced glutathione in the cytosol. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glutathione reductase from human erythrocytes was inhibited by incubation with the drugs 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea (HeCNU) under quasi-physiological conditions. For reference purposes, iodoacetamide was used for inactivating alkylation of the enzyme. In each case the modified glutathione reductase was crystallized and its structure determined. These analyses showed that in all experiments the enzyme had reacted at the distal sulfur, that is at the thiol of Cys-58, and virtually nowhere else in the visible structure. The electron density of the HeCNU derivative at 0.3 nm resolution is consistent with a 2-hydroxyethyl group. This alkyl moiety has recently been identified by chemical analysis [Schirmer, R. H., Schollhammer, T., Eisenbrand, G. and Krauth-Siegel, R. L. (1987) Free Radical Res. Commun. 3, 3-12]. The 0.2 nm resolution electron-density map of the BCNU-derivatized enzyme cannot be explained by a 2-hydroxyethyl group. Instead the modification appears as a carbamoyl moiety containing at least five non-hydrogen atoms. In this derivative the distal cysteine is forced into an unusual conformation.

Inhibition of human glutathione reductase by the nitrosourea drugs 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea. A crystallographic analysis.,Karplus PA, Krauth-Siegel RL, Schirmer RH, Schulz GE Eur J Biochem. 1988 Jan 15;171(1-2):193-8. PMID:3338461<ref>PMID:3338461</ref>

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

==See Also==
*[[Glutathione Reductase|Glutathione Reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Glutathione-disulfide reductase]]
[[Category: Large Structures]]
[[Category: Karplus, P A]]
[[Category: Schulz, G E]]
[[Category: Flavoenzyme]]
[[Category: Oxidoreductase]]