1SEP
MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN
Summary for 1SEP
| Entry DOI | 10.2210/pdb1sep/pdb |
| Descriptor | SEPIAPTERIN REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, BIOPTERIN, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, sepiapterin reductase, tetrahydrobiopterin |
| Biological source | Mus musculus (house mouse) |
| Cellular location | Cytoplasm: Q64105 |
| Total number of polymer chains | 1 |
| Total formula weight | 28889.62 |
| Authors | Auerbach, G.,Herrmann, A.,Guetlich, M.,Fischer, M.,Jacob, U.,Bacher, A.,Huber, R. (deposition date: 1997-05-23, release date: 1999-01-13, Last modification date: 2024-02-14) |
| Primary citation | Auerbach, G.,Herrmann, A.,Gutlich, M.,Fischer, M.,Jacob, U.,Bacher, A.,Huber, R. The 1.25 A crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters. EMBO J., 16:7219-7230, 1997 Cited by PubMed Abstract: 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. PubMed: 9405351DOI: 10.1093/emboj/16.24.7219 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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