1sep
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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 NAP and BIO 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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