1dnc: Difference between revisions

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[[Image:1dnc.gif|left|200px]]<br />

[[Image:1dnc.gif|left|200px]]<br /><applet load="1dnc" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1dnc" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1dnc, resolution 1.7Å" />

'''HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DIGLUTATHIONE-DINITROSO-IRON'''<br />

==Overview==

Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular, mechanisms by which it exerts its effects are largely unknown. Few, physiologic target molecules of NO have been identified, and even for, these, the modifications caused by NO remain uncharacterized. Human, glutathione reductase (hGR), a central enzyme of cellular antioxidant, defense, is inhibited by S-nitrosoglutathione (GSNO) and by, diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms, of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2, at 1.7 A resolution provide the first picture of enzyme inactivation by, NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is, oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas, modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid, (R-SO2H). Our results illustrate that various forms of NO can mediate, distinct chemistry, and that sulfhydryl oxidation must be considered as a, major mechanism of NO action.

Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular mechanisms by which it exerts its effects are largely unknown. Few physiologic target molecules of NO have been identified, and even for these, the modifications caused by NO remain uncharacterized. Human glutathione reductase (hGR), a central enzyme of cellular antioxidant defense, is inhibited by S-nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid (R-SO2H). Our results illustrate that various forms of NO can mediate distinct chemistry, and that sulfhydryl oxidation must be considered as a major mechanism of NO action.

==Disease==

Known ~~disease~~ associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138300 138300]]

Known diseases associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138300 138300]], Mental retardation, autosomal recessive, 6 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138244 138244]]

==About this Structure==

1DNC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4, FAD and GTT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutathione-disulfide_reductase Glutathione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.7 1.8.1.7] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1DNC OCA].

1DNC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=GTT:'>GTT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutathione-disulfide_reductase Glutathione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.7 1.8.1.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DNC OCA].

==Reference==

Line 19:

Line 18:

[[Category: Single protein]]

[[Category: Becker, K.]]

[[Category: Karplus, P.A.]]

[[Category: Karplus, P A.]]

[[Category: Keese, M.]]

[[Category: Savvides, S.N.]]

[[Category: Savvides, S N.]]

[[Category: Schirmer, R.H.]]

[[Category: Schirmer, R H.]]

[[Category: FAD]]

[[Category: GTT]]

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Line 30:

[[Category: sulfinic acid]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov~~ 12 16:34:~~05 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:18:25 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1dnc.gif|left|200px]]<br />
+[[Image:1dnc.gif|left|200px]]<br /><applet load="1dnc" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1dnc" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1dnc, resolution 1.7&Aring;" />
 '''HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DIGLUTATHIONE-DINITROSO-IRON'''<br />
 ==Overview==
-Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular, mechanisms by which it exerts its effects are largely unknown. Few, physiologic target molecules of NO have been identified, and even for, these, the modifications caused by NO remain uncharacterized. Human, glutathione reductase (hGR), a central enzyme of cellular antioxidant, defense, is inhibited by S-nitrosoglutathione (GSNO) and by, diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms, of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2, at 1.7 A resolution provide the first picture of enzyme inactivation by, NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is, oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas, modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid, (R-SO2H). Our results illustrate that various forms of NO can mediate, distinct chemistry, and that sulfhydryl oxidation must be considered as a, major mechanism of NO action.
+Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular mechanisms by which it exerts its effects are largely unknown. Few physiologic target molecules of NO have been identified, and even for these, the modifications caused by NO remain uncharacterized. Human glutathione reductase (hGR), a central enzyme of cellular antioxidant defense, is inhibited by S-nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid (R-SO2H). Our results illustrate that various forms of NO can mediate distinct chemistry, and that sulfhydryl oxidation must be considered as a major mechanism of NO action.
 ==Disease==
-Known disease associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138300 138300]]
+Known diseases associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138300 138300]], Mental retardation, autosomal recessive, 6 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138244 138244]]
 ==About this Structure==
-DNC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4, FAD and GTT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutathione-disulfide_reductase Glutathione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.7 1.8.1.7] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DNC OCA].
+DNC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=GTT:'>GTT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutathione-disulfide_reductase Glutathione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.7 1.8.1.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DNC OCA].
 ==Reference==
@@ Line 19: / Line 18: @@
 [[Category: Single protein]]
 [[Category: Becker, K.]]
-[[Category: Karplus, P.A.]]
+[[Category: Karplus, P A.]]
 [[Category: Keese, M.]]
-[[Category: Savvides, S.N.]]
+[[Category: Savvides, S N.]]
-[[Category: Schirmer, R.H.]]
+[[Category: Schirmer, R H.]]
 [[Category: FAD]]
 [[Category: GTT]]
@@ Line 31: / Line 30: @@
 [[Category: sulfinic acid]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:34:05 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:18:25 2008''