The various studies on tyrosinase have recently gained the attention of researchers due to their potential application values and the biological functions. In this study, we predicted the 3D structure of human tyrosinase and simulated the protein-protein interactions between tyrosinase and three binding partners, four and half LIM domains 2 (FHL2), cytochrome b-245 alpha polypeptide (CYBA), and RNA-binding motif protein 9 (RBM9). Our interaction simulations showed significant binding energy scores of ？595.3？kcal/mol for FHL2, ？859.1？kcal/mol for CYBA, and ？821.3？kcal/mol for RBM9. We also investigated the residues of each protein facing toward the predicted site of interaction with tyrosinase. Our computational predictions will be useful for elucidating the protein-protein interactions of tyrosinase and studying its binding mechanisms. 1. Introduction Tyrosinase (EC 1.14.18.1) is ubiquitously distributed in organisms and is a critical enzyme involved in melanin production, with multiple catalytic functions in pigment production [1–3]. Tyrosinase mutations are directly linked to pigmentation disorders in mammals [4, 5] and can cause a browning effect in vegetables [6, 7]. In addition, tyrosinase participates in cuticle formation in insects [8, 9]. In mammals, tyrosinase is a bifunctional enzyme that first converts tyrosine to DOPA and then to DOPA quinone, which is further cyclized and oxidized to produce melanin pigments [10]. The human tyrosinase protein contains two Cu2+-binding sites, two cysteine rich regions, a signal peptide region, a transmembrane anchor domain, and an EGF motif [11]. Two Cu2+ ions in the active site of tyrosinase are coordinated by three histidine residues each and are essential for the enzyme’s catalytic activity [12]. Furthermore, the presence of Cu2+ in the active site of tyrosinase is observed across numerous organisms [13]. Therefore, chelation of tyrosinase Cu2+ by synthetic compounds or agents from natural sources has been targeted as a way to block tyrosinase catalysis for medicinal purposes, darkening problems in agricultural products, and cosmetic interests [14, 15]. As the crystallographic structure of tyrosinase has been gradually elucidated, insights into its catalytic mechanisms and active site have also been revealed [16–18]. However, while the catalytic mechanism of tyrosinase-mediated melanin pigment production has been well studied, the relationship between tyrosinase enzyme activity and protein interactions has not been fully elucidated, despite several reports of interacting proteins for tyrosinase [19–22].
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