9EY8
Crystal structure of human tyrosinase-related protein 1 (TYRP1) in complex with (s)-amino-L-tyrosine
This is a non-PDB format compatible entry.
Summary for 9EY8
| Entry DOI | 10.2210/pdb9ey8/pdb |
| Descriptor | 5,6-dihydroxyindole-2-carboxylic acid oxidase, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (16 entities in total) |
| Functional Keywords | melanogenesis, human tyrosinase, tyrosinase inhibitor, metal binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 223727.82 |
| Authors | Ng, Y.M.,Soler-Lopez, M. (deposition date: 2024-04-09, release date: 2024-05-01, Last modification date: 2024-07-03) |
| Primary citation | Faure, C.,Min Ng, Y.,Belle, C.,Soler-Lopez, M.,Khettabi, L.,Saidi, M.,Berthet, N.,Maresca, M.,Philouze, C.,Rachidi, W.,Reglier, M.,du Moulinet d'Hardemare, A.,Jamet, H. Interactions of Phenylalanine Derivatives with Human Tyrosinase: Lessons from Experimental and Theoretical tudies. Chembiochem, 25:e202400235-e202400235, 2024 Cited by PubMed Abstract: The pigmentation of the skin, modulated by different actors in melanogenesis, is mainly due to the melanins (protective pigments). In humans, these pigments' precursors are synthetized by an enzyme known as tyrosinase (TyH). The regulation of the enzyme activity by specific modulators (inhibitors or activators) can offer a means to fight hypo- and hyper-pigmentations responsible for medical, psychological and societal handicaps. Herein, we report the investigation of phenylalanine derivatives as TyH modulators. Interacting with the binuclear copper active site of the enzyme, phenylalanine derivatives combine effects induced by combination with known resorcinol inhibitors and natural substrate/intermediate (amino acid part). Computational studies including docking, molecular dynamics and free energy calculations combined with biological activity assays on isolated TyH and in human melanoma MNT-1 cells, and X-ray crystallography analyses with the TyH analogue Tyrp1, provide conclusive evidence of the interactions of phenylalanine derivatives with human tyrosinase. In particular, our findings indicate that an analogue of L-DOPA, namely (S)-3-amino-tyrosine, stands out as an amino phenol derivative with inhibitory properties against TyH. PubMed: 38642076DOI: 10.1002/cbic.202400235 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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