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| {{STRUCTURE_1sep| PDB=1sep | SCENE= }} | | {{STRUCTURE_1sep| PDB=1sep | SCENE= }} |
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| '''MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN'''
| | ===MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_9405351}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 9405351 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_9405351}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Sepiapterin reductase]] | | [[Category: Sepiapterin reductase]] |
| [[Category: Tetrahydrobiopterin]] | | [[Category: Tetrahydrobiopterin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:36:51 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:27:43 2008'' |
