3HF6

Crystal structure of human tryptophan hydroxylase type 1 with bound LP-521834 and FE

3HF6 の概要

• エントリーDOI: 10.2210/pdb3hf6/pdb
• 分子名称: Tryptophan 5-hydroxylase 1, FE (III) ION, 4-(4-amino-6-{[(1R)-1-naphthalen-2-ylethyl]amino}-1,3,5-triazin-2-yl)-L-phenylalanine, ... (4 entities in total)
• 機能のキーワード: tryptophan 5-hydroxylase 1, alternative splicing, iron, metal-binding, monooxygenase, oxidoreductase, phosphoprotein, serotonin biosynthesis
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33772.24

構造登録者

Tari, L.W.,Swanson, R.V.,Hunter, M.J. (登録日: 2009-05-11, 公開日: 2009-11-24, 最終更新日: 2026-02-11)

主引用文献

Cianchetta, G.,Stouch, T.,Yu, W.,Shi, Z.-C.,Tari, L.W.,Swanson, R.V.,Hunter, M.J.,Hoffman, I.D.,Liu, Q.
Mechanism of Inhibition of Novel Tryptophan Hydroxylase Inhibitors Revealed by Co-crystal Structures and Kinetic Analysis
Curr Chem Genomics, 4:19-26, 2010

PubMed Abstract: Tryptophan hydroxylase (TPH) is a key enzyme in the synthesis of serotonin. As a neurotransmitter, serotonin plays important physiological roles both peripherally and centrally. Here we describe the discovery of substituted triazines as a novel class of tryptophan hydroxylase inhibitors. This class of TPH inhibitors can selectively reduce serotonin levels in murine intestine after oral administration without affecting levels in the brain. These TPH inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome.

PubMed: 19631532
DOI: 10.2174/1875397301004010019

実験手法

X-RAY DIFFRACTION (1.8 Å)