9J3U

Crystal structure of tyrosine phenol-lyase in complex with 3,5-dihydroxybenzoic acid

9J3U の概要

• エントリーDOI: 10.2210/pdb9j3u/pdb
• 分子名称: Tyrosine phenol-lyase, 3,5-DIHYDROXYBENZOATE, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: lyase, plp-dependent enzyme, pyridoxal-5'-phosphate, 3, 5-dihydroxybenzoic acid
• 由来する生物種: Morganella morganii subsp. morganii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 104779.68

構造登録者

Hara, K.,Kobayashi, T.,Ohishi, S.,Hashimoto, H.,Watanabe, K.,Miyoshi, N. (登録日: 2024-08-08, 公開日: 2025-04-23, 最終更新日: 2025-05-07)

主引用文献

Kobayashi, T.,Oishi, S.,Hara, K.,Matsui, M.,Mena, P.,Hashimoto, H.,Watanabe, K.,Miyoshi, N.
3,5-Dihydroxybenzoic Acid as a Potent Inhibitor of Tyrosine Phenol-Lyase Decreases Fecal Phenol Levels in Mice.
J.Med.Chem., 68:8786-8795, 2025

PubMed Abstract: Phenol is produced by β-elimination of l-tyrosine (Tyr) catalyzed by tyrosine phenol-lyase (TPL) during intestinal bacterial metabolism. Phenol and its conjugate, phenyl sulfate (PhS), are protein-bound uremic toxins (PBUTs). Elevated levels of phenol and PhS are strongly implicated in the etiology and outcomes of uremia. Because hemodialysis is insufficient in removing phenol and PhS, novel methods are necessary for inhibiting phenol production during bacterial metabolism. We explored TPL inhibitors and found that dietary polyphenols, particularly gallic acid (GA), strongly inhibited TPL-catalyzed phenol production. A GA derivative, 3,5-dihydroxybenzoic acid (3,5DHBA), competitively inhibited TPL and significantly decreased phenol levels in TPL-expressing bacteria ( and ) and Tyr-rich-diet-fed C57BL/6J mouse feces. Our findings suggested that 3,5DHBA was the most promising polyphenol in decreasing phenol levels. Therefore, dietary intake of 3,5DHBA or its phenolic precursors may be useful in minimizing PBUT levels by targeting intestinal bacteria.

PubMed: 40173106
DOI: 10.1021/acs.jmedchem.5c00418

実験手法

X-RAY DIFFRACTION (1.83 Å)