9ey5

Crystal structure of human tyrosinase-related protein 1 (TYRP1) in complex with (S)-2,4-dihydroxyphenylalanine

spinqualitylabelsall models 9ey5, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ey5 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.61Å Ligands: BMA, FUC, GOL, MAN, NAG, OTY, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TYRP1_HUMAN Oculocutaneous albinism type 3. The disease is caused by mutations affecting the gene represented in this entry. Function TYRP1_HUMAN Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. May regulate or influence the type of melanin synthesized. Also to a lower extent, capable of hydroxylating tyrosine and producing melanin.[UniProtKB:P07147] Publication Abstract from PubMed 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. Interactions of phenylalanine derivatives with human tyrosinase: lessons from experimental and theoretical studies.,Faure C, Ng YM, Belle C, Soler-Lopez M, Khettabi L, Saidi M, Berthet N, Maresca M, Philouze C, Rachidi W, Reglier M, du Moullinet d'Hardemare A, Jamet H Chembiochem. 2024 Apr 20:e202400235. doi: 10.1002/cbic.202400235. PMID:38642076 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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