1yfx
From Proteopedia
(New page: 200px<br /><applet load="1yfx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yfx, resolution 2.00Å" /> '''Crystal structure of...) |
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| - | [[Image:1yfx.gif|left|200px]]<br /><applet load="1yfx" size=" | + | [[Image:1yfx.gif|left|200px]]<br /><applet load="1yfx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1yfx, resolution 2.00Å" /> | caption="1yfx, resolution 2.00Å" /> | ||
'''Crystal structure of 3-hydroxyanthranilate-3,4-dioxygenase from Ralstonia metallidurans complexed with 4-chloro-3-hydroxyanthranilic acid and NO'''<br /> | '''Crystal structure of 3-hydroxyanthranilate-3,4-dioxygenase from Ralstonia metallidurans complexed with 4-chloro-3-hydroxyanthranilic acid and NO'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 3-Hydroxyanthranilate-3,4-dioxygenase (HAD) catalyzes the oxidative ring | + | 3-Hydroxyanthranilate-3,4-dioxygenase (HAD) catalyzes the oxidative ring opening of 3-hydroxyanthranilate in the final enzymatic step of the biosynthetic pathway from tryptophan to quinolinate, the universal de novo precursor to the pyridine ring of nicotinamide adenine dinucleotide. The enzyme requires Fe2+ as a cofactor and is inactivated by 4-chloro-3-hydroxyanthranilate. HAD from Ralstonia metallidurans was crystallized, and the structure was determined at 1.9 A resolution. The structures of HAD complexed with the inhibitor 4-chloro-3-hydroxyanthranilic acid and either molecular oxygen or nitric oxide were determined at 2.0 A resolution, and the structure of HAD complexed with 3-hydroxyanthranilate was determined at 3.2 A resolution. HAD is a homodimer with a subunit topology that is characteristic of the cupin barrel fold. Each monomer contains two iron binding sites. The catalytic iron is buried deep inside the beta-barrel with His51, Glu57, and His95 serving as ligands. The other iron site forms an FeS4 center close to the solvent surface in which the sulfur atoms are provided by Cys125, Cys128, Cys162, and Cys165. The two iron sites are separated by 24 A. On the basis of the crystal structures of HAD, mutagenesis studies were carried out in order to elucidate the enzyme mechanism. In addition, a new mechanism for the enzyme inactivation by 4-chloro-3-hydroxyanthranilate is proposed. |
==About this Structure== | ==About this Structure== | ||
| - | 1YFX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cupriavidus_metallidurans Cupriavidus metallidurans] with FE, NO, TRS and 4AA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-hydroxyanthranilate_3,4-dioxygenase 3-hydroxyanthranilate 3,4-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.6 1.13.11.6] Full crystallographic information is available from [http:// | + | 1YFX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cupriavidus_metallidurans Cupriavidus metallidurans] with <scene name='pdbligand=FE:'>FE</scene>, <scene name='pdbligand=NO:'>NO</scene>, <scene name='pdbligand=TRS:'>TRS</scene> and <scene name='pdbligand=4AA:'>4AA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-hydroxyanthranilate_3,4-dioxygenase 3-hydroxyanthranilate 3,4-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.6 1.13.11.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YFX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Cupriavidus metallidurans]] | [[Category: Cupriavidus metallidurans]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Begley, T | + | [[Category: Begley, T P.]] |
| - | [[Category: Colabroy, K | + | [[Category: Colabroy, K L.]] |
| - | [[Category: Ealick, S | + | [[Category: Ealick, S E.]] |
[[Category: Zhang, Y.]] | [[Category: Zhang, Y.]] | ||
[[Category: 4AA]] | [[Category: 4AA]] | ||
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[[Category: cupin]] | [[Category: cupin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:04:58 2008'' |
Revision as of 14:04, 21 February 2008
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Crystal structure of 3-hydroxyanthranilate-3,4-dioxygenase from Ralstonia metallidurans complexed with 4-chloro-3-hydroxyanthranilic acid and NO
Overview
3-Hydroxyanthranilate-3,4-dioxygenase (HAD) catalyzes the oxidative ring opening of 3-hydroxyanthranilate in the final enzymatic step of the biosynthetic pathway from tryptophan to quinolinate, the universal de novo precursor to the pyridine ring of nicotinamide adenine dinucleotide. The enzyme requires Fe2+ as a cofactor and is inactivated by 4-chloro-3-hydroxyanthranilate. HAD from Ralstonia metallidurans was crystallized, and the structure was determined at 1.9 A resolution. The structures of HAD complexed with the inhibitor 4-chloro-3-hydroxyanthranilic acid and either molecular oxygen or nitric oxide were determined at 2.0 A resolution, and the structure of HAD complexed with 3-hydroxyanthranilate was determined at 3.2 A resolution. HAD is a homodimer with a subunit topology that is characteristic of the cupin barrel fold. Each monomer contains two iron binding sites. The catalytic iron is buried deep inside the beta-barrel with His51, Glu57, and His95 serving as ligands. The other iron site forms an FeS4 center close to the solvent surface in which the sulfur atoms are provided by Cys125, Cys128, Cys162, and Cys165. The two iron sites are separated by 24 A. On the basis of the crystal structures of HAD, mutagenesis studies were carried out in order to elucidate the enzyme mechanism. In addition, a new mechanism for the enzyme inactivation by 4-chloro-3-hydroxyanthranilate is proposed.
About this Structure
1YFX is a Single protein structure of sequence from Cupriavidus metallidurans with , , and as ligands. Active as 3-hydroxyanthranilate 3,4-dioxygenase, with EC number 1.13.11.6 Full crystallographic information is available from OCA.
Reference
Structural studies on 3-hydroxyanthranilate-3,4-dioxygenase: the catalytic mechanism of a complex oxidation involved in NAD biosynthesis., Zhang Y, Colabroy KL, Begley TP, Ealick SE, Biochemistry. 2005 May 31;44(21):7632-43. PMID:15909978
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