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==MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN==
==MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN==
<StructureSection load='1sep' size='340' side='right' caption='[[1sep]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
<StructureSection load='1sep' size='340' side='right'caption='[[1sep]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1sep]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. The August 2015 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Tetrahydrobiopterin Biosynthesis''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2015_8 10.2210/rcsb_pdb/mom_2015_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SEP FirstGlance]. <br>
<table><tr><td colspan='2'>[[1sep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The August 2015 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Tetrahydrobiopterin Biosynthesis''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2015_8 10.2210/rcsb_pdb/mom_2015_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SEP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BIO:BIOPTERIN'>BIO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 1.95&#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=BIO:BIOPTERIN'>BIO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=1sep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sep OCA], [http://pdbe.org/1sep PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1sep RCSB], [http://www.ebi.ac.uk/pdbsum/1sep PDBsum]</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=1sep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sep OCA], [https://pdbe.org/1sep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sep RCSB], [https://www.ebi.ac.uk/pdbsum/1sep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sep 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]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/se/1sep_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/se/1sep_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
Line 19: Line 20:
</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=1sep 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=1sep ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<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 1sep" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Tetrahydrobiopterin Biosynthesis]]
[[Category: Tetrahydrobiopterin Biosynthesis]]
[[Category: Auerbach, G]]
[[Category: Auerbach G]]
[[Category: Bacher, A]]
[[Category: Bacher A]]
[[Category: Fischer, M]]
[[Category: Fischer M]]
[[Category: Guetlich, M]]
[[Category: Guetlich M]]
[[Category: Herrmann, A]]
[[Category: Herrmann A]]
[[Category: Huber, R]]
[[Category: Huber R]]
[[Category: Jacob, U]]
[[Category: Jacob U]]
[[Category: Oxidoreductase]]
[[Category: Sepiapterin reductase]]
[[Category: Tetrahydrobiopterin]]

Latest revision as of 11:30, 14 February 2024

MOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERINMOUSE SEPIAPTERIN REDUCTASE COMPLEXED WITH NADP AND SEPIAPTERIN

Structural highlights

1sep is a 1 chain structure with sequence from Mus musculus. The August 2015 RCSB PDB Molecule of the Month feature on Tetrahydrobiopterin Biosynthesis by David Goodsell is 10.2210/rcsb_pdb/mom_2015_8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.95Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPRE_MOUSE Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

1sep, resolution 1.95Å

Drag the structure with the mouse to rotate

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OCA
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