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5j6d
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Discovery of acyl guanidine tryptophan hydroxylase-1 inhibitors== | |
| + | <StructureSection load='5j6d' size='340' side='right' caption='[[5j6d]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5j6d]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J6D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J6D FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6H5:4-[(N-{[2-(3-METHOXYPHENOXY)-6-(PIPERIDIN-1-YL)PHENYL]METHYL}CARBAMIMIDOYL)CARBAMOYL]-L-PHENYLALANINE'>6H5</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptophan_5-monooxygenase Tryptophan 5-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.16.4 1.14.16.4] </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=5j6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j6d OCA], [http://pdbe.org/5j6d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j6d RCSB], [http://www.ebi.ac.uk/pdbsum/5j6d PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | An increasing number of diseases have been linked to a dysfunctional peripheral serotonin system. Given that tryptophan hydroxylase 1 (TPH1) is the rate limiting enzyme in the biosynthesis off serotonin, it represents an attractive target to regulate peripheral serotonin. Following up to our first disclosure, we report a new chemotype of TPH1 inhibitors where-by the more common central planar heterocycle has been replaced with an open-chain, acyl guanidine surrogate. Through our work, we found that compounds of this nature provide highly potent TPH1 inhibitors with favorable physicochemical properties that were effective in reducing murine intestinal 5-HT in vivo. Furthermore, we obtained a high resolution (1.90A) X-ray structure crystal structure of one of these inhibitors (compound 51) that elucidated the active conformation along with revealing a dimeric form of TPH1 for the first time. | ||
| - | + | Discovery of acyl guanidine tryptophan hydroxylase-1 inhibitors.,Goldberg DR, De Lombaert S, Aiello R, Bourassa P, Barucci N, Zhang Q, Paralkar V, Stein AJ, Valentine J, Zavadoski W Bioorg Med Chem Lett. 2016 Jun 15;26(12):2855-60. doi:, 10.1016/j.bmcl.2016.04.057. Epub 2016 Apr 21. PMID:27146606<ref>PMID:27146606</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5j6d" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Tryptophan 5-monooxygenase]] | ||
| + | [[Category: Goldberg, D R]] | ||
| + | [[Category: Lombaert, S De]] | ||
| + | [[Category: Stein, A J]] | ||
| + | [[Category: Acyl]] | ||
| + | [[Category: Iron]] | ||
| + | [[Category: Oxidoreductase-inhibitor complex]] | ||
| + | [[Category: Quanidine]] | ||
| + | [[Category: Tph1]] | ||
Revision as of 23:03, 1 June 2016
Discovery of acyl guanidine tryptophan hydroxylase-1 inhibitors
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