9J3U
Crystal structure of tyrosine phenol-lyase in complex with 3,5-dihydroxybenzoic acid
Summary for 9J3U
| Entry DOI | 10.2210/pdb9j3u/pdb |
| Descriptor | Tyrosine phenol-lyase, 3,5-DIHYDROXYBENZOATE, POTASSIUM ION, ... (4 entities in total) |
| Functional Keywords | lyase, plp-dependent enzyme, pyridoxal-5'-phosphate, 3, 5-dihydroxybenzoic acid |
| Biological source | Morganella morganii subsp. morganii |
| Total number of polymer chains | 2 |
| Total formula weight | 104779.68 |
| Authors | Hara, K.,Kobayashi, T.,Ohishi, S.,Hashimoto, H.,Watanabe, K.,Miyoshi, N. (deposition date: 2024-08-08, release date: 2025-04-23, Last modification date: 2025-05-07) |
| Primary citation | 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 Cited by 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: 40173106DOI: 10.1021/acs.jmedchem.5c00418 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.83 Å) |
Structure validation
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