2huo: Difference between revisions

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[[Image:2huo.gif|left|200px]]<br /><applet load="2huo" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:2huo.gif|left|200px]]<br /><applet load="2huo" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2huo, resolution 2.00Å" />

'''Crystal structure of mouse myo-inositol oxygenase in complex with substrate'''<br />

==Overview==

Altered metabolism of the inositol sugars myo-inositol (MI) and, d-chiro-inositol is implicated in diabetic complications. In animals, catabolism of MI and D-chiro-inositol depends on the enzyme MI oxygenase, (MIOX), which catalyzes the first committed step of the, glucuronate-xylulose pathway, and is found almost exclusively in the, kidneys. The crystal structure of MIOX, in complex with MI, has been, determined by multiwavelength anomalous diffraction methods and refined at, 2.0-A resolution (R=0.206, Rfree=0.253). The structure reveals a, monomeric, single-domain protein with a mostly helical fold that is, distantly related to the diverse HD domain superfamily. Five helices form, the structural core and provide six ligands (four His and two Asp) for the, di-iron center, in which the two iron atoms are bridged by a putative, hydroxide ion and one of the Asp ligands, Asp-124. A key loop forms a lid, over the MI substrate, which is coordinated in bidentate mode to one iron, atom. It is proposed that this mode of iron coordination, and interaction, with a key Lys residue, activate MI for bond cleavage. The structure also, reveals the basis of substrate specificity and suggests routes for the, development of specific MIOX inhibitors.

Altered metabolism of the inositol sugars myo-inositol (MI) and d-chiro-inositol is implicated in diabetic complications. In animals, catabolism of MI and D-chiro-inositol depends on the enzyme MI oxygenase (MIOX), which catalyzes the first committed step of the glucuronate-xylulose pathway, and is found almost exclusively in the kidneys. The crystal structure of MIOX, in complex with MI, has been determined by multiwavelength anomalous diffraction methods and refined at 2.0-A resolution (R=0.206, Rfree=0.253). The structure reveals a monomeric, single-domain protein with a mostly helical fold that is distantly related to the diverse HD domain superfamily. Five helices form the structural core and provide six ligands (four His and two Asp) for the di-iron center, in which the two iron atoms are bridged by a putative hydroxide ion and one of the Asp ligands, Asp-124. A key loop forms a lid over the MI substrate, which is coordinated in bidentate mode to one iron atom. It is proposed that this mode of iron coordination, and interaction with a key Lys residue, activate MI for bond cleavage. The structure also reveals the basis of substrate specificity and suggests routes for the development of specific MIOX inhibitors.

==About this Structure==

2HUO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with FE, OH, INS and FMT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol_oxygenase Inositol oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.99.1 1.13.99.1] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2HUO OCA].

2HUO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=FE:'>FE</scene>, <scene name='pdbligand=OH:'>OH</scene>, <scene name='pdbligand=INS:'>INS</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol_oxygenase Inositol oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.99.1 1.13.99.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HUO OCA].

==Reference==

Line 14:

[[Category: Mus musculus]]

[[Category: Single protein]]

[[Category: Baker, E.N.]]

[[Category: Baker, E N.]]

[[Category: Brown, P.M.]]

[[Category: Brown, P M.]]

[[Category: Caradoc-Davies, T.T.]]

[[Category: Caradoc-Davies, T T.]]

[[Category: Cooper, G.J.S.]]

[[Category: Cooper, G J.S.]]

[[Category: Dickson, J.M.J.]]

[[Category: Dickson, J M.J.]]

[[Category: Loomes, K.M.]]

[[Category: Loomes, K M.]]

[[Category: FE]]

[[Category: FMT]]

Line 27:

[[Category: protein-substrate complex]]

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@@ Line 1: / Line 1: @@
-[[Image:2huo.gif|left|200px]]<br /><applet load="2huo" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2huo.gif|left|200px]]<br /><applet load="2huo" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2huo, resolution 2.00&Aring;" />
 '''Crystal structure of mouse myo-inositol oxygenase in complex with substrate'''<br />
 ==Overview==
-Altered metabolism of the inositol sugars myo-inositol (MI) and, d-chiro-inositol is implicated in diabetic complications. In animals, catabolism of MI and D-chiro-inositol depends on the enzyme MI oxygenase, (MIOX), which catalyzes the first committed step of the, glucuronate-xylulose pathway, and is found almost exclusively in the, kidneys. The crystal structure of MIOX, in complex with MI, has been, determined by multiwavelength anomalous diffraction methods and refined at, 2.0-A resolution (R=0.206, Rfree=0.253). The structure reveals a, monomeric, single-domain protein with a mostly helical fold that is, distantly related to the diverse HD domain superfamily. Five helices form, the structural core and provide six ligands (four His and two Asp) for the, di-iron center, in which the two iron atoms are bridged by a putative, hydroxide ion and one of the Asp ligands, Asp-124. A key loop forms a lid, over the MI substrate, which is coordinated in bidentate mode to one iron, atom. It is proposed that this mode of iron coordination, and interaction, with a key Lys residue, activate MI for bond cleavage. The structure also, reveals the basis of substrate specificity and suggests routes for the, development of specific MIOX inhibitors.
+Altered metabolism of the inositol sugars myo-inositol (MI) and d-chiro-inositol is implicated in diabetic complications. In animals, catabolism of MI and D-chiro-inositol depends on the enzyme MI oxygenase (MIOX), which catalyzes the first committed step of the glucuronate-xylulose pathway, and is found almost exclusively in the kidneys. The crystal structure of MIOX, in complex with MI, has been determined by multiwavelength anomalous diffraction methods and refined at 2.0-A resolution (R=0.206, Rfree=0.253). The structure reveals a monomeric, single-domain protein with a mostly helical fold that is distantly related to the diverse HD domain superfamily. Five helices form the structural core and provide six ligands (four His and two Asp) for the di-iron center, in which the two iron atoms are bridged by a putative hydroxide ion and one of the Asp ligands, Asp-124. A key loop forms a lid over the MI substrate, which is coordinated in bidentate mode to one iron atom. It is proposed that this mode of iron coordination, and interaction with a key Lys residue, activate MI for bond cleavage. The structure also reveals the basis of substrate specificity and suggests routes for the development of specific MIOX inhibitors.
 ==About this Structure==
-HUO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with FE, OH, INS and FMT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol_oxygenase Inositol oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.99.1 1.13.99.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HUO OCA].
+HUO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=FE:'>FE</scene>, <scene name='pdbligand=OH:'>OH</scene>, <scene name='pdbligand=INS:'>INS</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol_oxygenase Inositol oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.99.1 1.13.99.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HUO OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Mus musculus]]
 [[Category: Single protein]]
-[[Category: Baker, E.N.]]
+[[Category: Baker, E N.]]
-[[Category: Brown, P.M.]]
+[[Category: Brown, P M.]]
-[[Category: Caradoc-Davies, T.T.]]
+[[Category: Caradoc-Davies, T T.]]
-[[Category: Cooper, G.J.S.]]
+[[Category: Cooper, G J.S.]]
-[[Category: Dickson, J.M.J.]]
+[[Category: Dickson, J M.J.]]
-[[Category: Loomes, K.M.]]
+[[Category: Loomes, K M.]]
 [[Category: FE]]
 [[Category: FMT]]
@@ Line 27: / Line 27: @@
 [[Category: protein-substrate complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:59:45 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:45:55 2008''