4j7u

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'''Unreleased structure'''
 
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The entry 4j7u is ON HOLD until Paper Publication
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==Crystal structure of human sepiapterin reductase in complex with sulfathiazole==
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<StructureSection load='4j7u' size='340' side='right'caption='[[4j7u]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4j7u]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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=4J7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J7U FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.44&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YTZ:4-AMINO-N-(1,3-THIAZOL-2-YL)BENZENESULFONAMIDE'>YTZ</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4j7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7u OCA], [https://pdbe.org/4j7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j7u RCSB], [https://www.ebi.ac.uk/pdbsum/4j7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j7u ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/SPRE_HUMAN SPRE_HUMAN] Defects in SPR are the cause of dystonia DOPA-responsive due to sepiapterin reductase deficiency (DRDSPRD) [MIM:[https://omim.org/entry/612716 612716]. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity. Cognitive anomalies are also often present. The disease is due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures.<ref>PMID:11443547</ref> <ref>PMID:16650784</ref> <ref>PMID:17159114</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/SPRE_HUMAN SPRE_HUMAN] Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase. Crystal structures of sepiapterin reductase with bound sulfa drugs reveal how structurally diverse sulfa drugs achieve specific inhibition of the enzyme. The effect of sulfa drugs on tetrahydrobiopterin-dependent neurotransmitter biosynthesis in cell-based assays provides a rationale for some of their central nervous system-related side effects, particularly in high-dose sulfamethoxazole therapy of Pneumocystis pneumonia. Our findings reveal an unexpected aspect of the pharmacology of sulfa drugs and might translate into their improved medical use.
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Authors: Groenlund Pedersen, M., Pojer, F., Johnsson, K.
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Tetrahydrobiopterin biosynthesis as an off-target of sulfa drugs.,Haruki H, Pedersen MG, Gorska KI, Pojer F, Johnsson K Science. 2013 May 24;340(6135):987-91. doi: 10.1126/science.1232972. PMID:23704574<ref>PMID:23704574</ref>
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Description: Crystal structure of human sepiapterin reductase in complex with sulfathiazole
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4j7u" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Tetrahydrobiopterin Biosynthesis]]
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[[Category: Groenlund Pedersen M]]
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[[Category: Johnsson K]]
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[[Category: Pojer F]]

Current revision

Crystal structure of human sepiapterin reductase in complex with sulfathiazole

PDB ID 4j7u

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