6i6c: Difference between revisions

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-'''Unreleased structure'''
-The entry 6i6c is ON HOLD  until Paper Publication
+==SEPIAPTERIN REDUCTASE IN COMPLEX WITH COMPOUND 2==
+<StructureSection load='6i6c' size='340' side='right'caption='[[6i6c]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6i6c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I6C FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=H4H:(1~{R},2~{S},4~{S})-~{N}-(3-chloranyl-4-cyano-phenyl)sulfonylbicyclo[2.2.1]heptane-2-carboxamide'>H4H</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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='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=6i6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i6c OCA], [http://pdbe.org/6i6c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i6c RCSB], [http://www.ebi.ac.uk/pdbsum/6i6c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i6c ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://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:[http://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>
+== Function ==
+[[http://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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Genome-wide-association studies in chronic low back pain patients identified sepiapterin reductase as a high interest target for developing new analgesics. Here we used (19)F NMR fragment screening for the discovery of novel, ligand-efficient SPR inhibitors. We report the crystal structures of six chemically diverse inhibitors complexed with SPR, identifying relevant interactions and binding modes in the sepiapterin pocket. Exploration of our initial fragment screening hit led to double-digit nanomolar inhibitors of SPR with excellent ligand efficiency.
-Authors: Alen, J., Schade, M., Wagener, M., Blaesse, M.
+Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors.,Alen J, Schade M, Wagener M, Christian F, Nordhoff S, Merla B, Dunkern TR, Bahrenberg G, Ratcliffe P J Med Chem. 2019 Jun 25. doi: 10.1021/acs.jmedchem.9b00218. PMID:31244106<ref>PMID:31244106</ref>
-Description: SEPIAPTERIN REDUCTASE IN COMPLEX WITH COMPOUND 2
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6i6c" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Alen, J]]
+[[Category: Blaesse, M]]
 [[Category: Schade, M]]
 [[Category: Wagener, M]]
-[[Category: Blaesse, M]]
+[[Category: Oxidoreductase]]
-[[Category: Alen, J]]
+[[Category: Proteros biostructures gmbh]]
+[[Category: Sepiapterin-reductase]]