1sep: Difference between revisions
New page: left|200px<br /><applet load="1sep" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sep, resolution 1.95Å" /> '''MOUSE SEPIAPTERIN RE... |
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[[Image:1sep.jpg|left|200px]]<br /><applet load="1sep" size=" | [[Image:1sep.jpg|left|200px]]<br /><applet load="1sep" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1sep, resolution 1.95Å" /> | caption="1sep, resolution 1.95Å" /> | ||
'''MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN'''<br /> | '''MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN'''<br /> | ||
==Overview== | ==Overview== | ||
Sepiapterin reductase catalyses the last steps in the biosynthesis of | Sepiapterin reductase catalyses the last steps in the biosynthesis of tetrahydrobiopterin, the essential co-factor of aromatic amino acid hydroxylases and nitric oxide synthases. We have determined the crystal structure of mouse sepiapterin reductase by multiple isomorphous replacement at a resolution of 1.25 A in its ternary complex with oxaloacetate and NADP. The homodimeric structure reveals a single-domain alpha/beta-fold with a central four-helix bundle connecting two seven-stranded parallel beta-sheets, each sandwiched between two arrays of three helices. Ternary complexes with the substrate sepiapterin or the product tetrahydrobiopterin were studied. Each subunit contains a specific aspartate anchor (Asp258) for pterin-substrates, which positions the substrate side chain C1'-carbonyl group near Tyr171 OH and NADP C4'N. The catalytic mechanism of SR appears to consist of a NADPH-dependent proton transfer from Tyr171 to the substrate C1' and C2' carbonyl functions accompanied by stereospecific side chain isomerization. Complex structures with the inhibitor N-acetyl serotonin show the indoleamine bound such that both reductase and isomerase activity for pterins is inhibited, but reaction with a variety of carbonyl compounds is possible. The complex structure with N-acetyl serotonin suggests the possibility for a highly specific feedback regulatory mechanism between the formation of indoleamines and pteridines in vivo. | ||
==About this Structure== | ==About this Structure== | ||
1SEP 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 NAP and BIO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Sepiapterin_reductase Sepiapterin reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.153 1.1.1.153] Full crystallographic information is available from [http:// | 1SEP 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=NAP:'>NAP</scene> and <scene name='pdbligand=BIO:'>BIO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Sepiapterin_reductase Sepiapterin reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.153 1.1.1.153] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEP OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: tetrahydrobiopterin]] | [[Category: tetrahydrobiopterin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:43 2008'' | ||
Revision as of 16:00, 21 February 2008
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MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN
OverviewOverview
Sepiapterin reductase catalyses the last steps in the biosynthesis of tetrahydrobiopterin, the essential co-factor of aromatic amino acid hydroxylases and nitric oxide synthases. We have determined the crystal structure of mouse sepiapterin reductase by multiple isomorphous replacement at a resolution of 1.25 A in its ternary complex with oxaloacetate and NADP. The homodimeric structure reveals a single-domain alpha/beta-fold with a central four-helix bundle connecting two seven-stranded parallel beta-sheets, each sandwiched between two arrays of three helices. Ternary complexes with the substrate sepiapterin or the product tetrahydrobiopterin were studied. Each subunit contains a specific aspartate anchor (Asp258) for pterin-substrates, which positions the substrate side chain C1'-carbonyl group near Tyr171 OH and NADP C4'N. The catalytic mechanism of SR appears to consist of a NADPH-dependent proton transfer from Tyr171 to the substrate C1' and C2' carbonyl functions accompanied by stereospecific side chain isomerization. Complex structures with the inhibitor N-acetyl serotonin show the indoleamine bound such that both reductase and isomerase activity for pterins is inhibited, but reaction with a variety of carbonyl compounds is possible. The complex structure with N-acetyl serotonin suggests the possibility for a highly specific feedback regulatory mechanism between the formation of indoleamines and pteridines in vivo.
About this StructureAbout this Structure
1SEP is a Single protein structure of sequence from Mus musculus with and as ligands. Active as Sepiapterin reductase, with EC number 1.1.1.153 Full crystallographic information is available from OCA.
ReferenceReference
The 1.25 A crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters., Auerbach G, Herrmann A, Gutlich M, Fischer M, Jacob U, Bacher A, Huber R, EMBO J. 1997 Dec 15;16(24):7219-30. PMID:9405351
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