7zih: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7zih]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZIH FirstGlance]. <br> | <table><tr><td colspan='2'>[[7zih]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZIH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JCR:8-(1~{H}-benzimidazol-2-ylmethyl)-3-ethyl-7-(phenylmethyl)purine-2,6-dione'>JCR</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.4689083Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JCR:8-(1~{H}-benzimidazol-2-ylmethyl)-3-ethyl-7-(phenylmethyl)purine-2,6-dione'>JCR</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=7zih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zih OCA], [https://pdbe.org/7zih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zih RCSB], [https://www.ebi.ac.uk/pdbsum/7zih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zih 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=7zih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zih OCA], [https://pdbe.org/7zih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zih RCSB], [https://www.ebi.ac.uk/pdbsum/7zih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zih ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/TPH1_HUMAN TPH1_HUMAN] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 7zih" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7zih" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Hydroxylases 3D structures|Hydroxylases 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 16:32, 1 February 2024
Crystal structure of human tryptophan hydroxylase 1 in complex with inhibitor AG-01-128Crystal structure of human tryptophan hydroxylase 1 in complex with inhibitor AG-01-128
Structural highlights
FunctionPublication Abstract from PubMedTryptophan hydroxylases catalyze the first and rate-limiting step in the synthesis of serotonin. Serotonin is a key neurotransmitter in the central nervous system and, in the periphery, functions as a local hormone with multiple physiological functions. Studies in genetically altered mouse models have shown that dysregulation of peripheral serotonin levels leads to metabolic, inflammatory, and fibrotic diseases. Overproduction of serotonin by tumor cells causes severe symptoms typical for the carcinoid syndrome, and tryptophan hydroxylase inhibitors are already in clinical use for patients suffering from this disease. Here, we describe a novel class of potent tryptophan hydroxylase inhibitors, characterized by spanning all active binding sites important for catalysis, specifically those of the cosubstrate pterin, the substrate tryptophan as well as directly chelating the catalytic iron ion. The inhibitors were designed to efficiently reduce serotonin in the periphery while not passing the blood-brain barrier, thus preserving serotonin levels in the brain. Structure-Based Design of Xanthine-Benzimidazole Derivatives as Novel and Potent Tryptophan Hydroxylase Inhibitors.,Specker E, Matthes S, Wesolowski R, Schutz A, Grohmann M, Alenina N, Pleimes D, Mallow K, Neuenschwander M, Gogolin A, Weise M, Pfeifer J, Ziebart N, Heinemann U, von Kries JP, Nazare M, Bader M J Med Chem. 2022 Aug 25;65(16):11126-11149. doi: 10.1021/acs.jmedchem.2c00598., Epub 2022 Aug 3. PMID:35921615[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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