View source for 5j6d


==Discovery of acyl guanidine tryptophan hydroxylase-1 inhibitors==
<StructureSection load='5j6d' size='340' side='right'caption='[[5j6d]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5j6d]] is a 2 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=5J6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J6D FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5j6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j6d OCA], [https://pdbe.org/5j6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j6d RCSB], [https://www.ebi.ac.uk/pdbsum/5j6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j6d ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TPH1_HUMAN TPH1_HUMAN] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5j6d" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hydroxylases 3D structures|Hydroxylases 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: De Lombaert S]]
[[Category: Goldberg DR]]
[[Category: Stein AJ]]