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==SEPIAPTERIN REDUCTASE COMPLEXED WITH N-ACETYL SEROTONIN==
==SEPIAPTERIN REDUCTASE COMPLEXED WITH N-ACETYL SEROTONIN==
<StructureSection load='1nas' size='340' side='right' caption='[[1nas]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='1nas' size='340' side='right'caption='[[1nas]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1nas]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NAS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NAS FirstGlance]. <br>
<table><tr><td colspan='2'>[[1nas]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NAS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NAS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASE:N-ACETYL+SEROTONIN'>ASE</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sepiapterin_reductase_(L-erythro-7,8-dihydrobiopterin_forming) Sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.153 1.1.1.153] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASE:N-ACETYL+SEROTONIN'>ASE</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nas OCA], [http://pdbe.org/1nas PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nas RCSB], [http://www.ebi.ac.uk/pdbsum/1nas PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1nas ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nas OCA], [https://pdbe.org/1nas PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nas RCSB], [https://www.ebi.ac.uk/pdbsum/1nas PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nas ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SPRE_MOUSE SPRE_MOUSE]] Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.  
[https://www.uniprot.org/uniprot/SPRE_MOUSE SPRE_MOUSE] Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nas ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nas ConSurf].
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 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<ref>PMID:9405351</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1nas" style="background-color:#fffaf0;"></div>
==See Also==
*[[InhA|InhA]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Auerbach, G]]
[[Category: Mus musculus]]
[[Category: Bacher, A]]
[[Category: Auerbach G]]
[[Category: Herrmann, A]]
[[Category: Bacher A]]
[[Category: Huber, R]]
[[Category: Herrmann A]]
[[Category: N-acetyl serotonin]]
[[Category: Huber R]]
[[Category: Oxidoreductase]]
[[Category: Sdr family]]
[[Category: Sepiapterin reductase]]
[[Category: Short-chain dehydrogenase]]
[[Category: Tetrahydrobiopterin]]

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