Structural characterization of tyrosinases and an update on human enzymes.

Tyrosinase, a pivotal enzyme in melanin biosynthesis, orchestrates the pigmentation process in humans, affecting skin, hair, and eye color. This chapter examines the three-dimensional structure and functional aspects of tyrosinases from various sources, highlighting their di-metal ion coordination crucial for catalytic activity. I explore the biochemical pathwayscheme catalyzed by tyrosinase, specifically the oxidation of L-tyrosine to L-dopaquinone, a precursor in melanin synthesis. Detailed structural analyses, including 3D structures obtained from X-ray crystallography and computational modeling, reveal key insights into the enzyme's active site, variations among tyrosinases, and substrate binding mechanisms. Furthermore, the chapter investigates the role of human tyrosinase variants, their inhibitors, essential for developing therapeutic and cosmetic applications targeting hyperpigmentation disorders. Structural characterizations of tyrosinase-inhibitor complexes provide a foundation for designing effective inhibitors, with compounds like kojic acid, L-mimosine, and (S)-3-amino-tyrosine demonstrating significant inhibitory potential. This comprehensive examination of the structure, function, and inhibition mechanisms of tyrosinase offers avenues for innovative treatments in biotechnology, health, and beyond.

Designed Rubredoxin miniature in a fully artificial electron chain triggered by visible light.

Designing metal sites into de novo proteins has significantly improved, recently. However, identifying the minimal coordination spheres, able to encompass the necessary information for metal binding and activity, still represents a great challenge, today. Here, we test our understanding with a benchmark, nevertheless difficult, case. We assemble into a miniature 28-residue protein, the quintessential elements required to fold properly around a FeCys4 redox center, and to function efficiently in electron-transfer. This study addresses a challenge in de novo protein design, as it reports the crystal structure of a designed tetra-thiolate metal-binding protein in sub-Å agreement with the intended design. This allows us to well correlate structure to spectroscopic and electrochemical properties. Given its high reduction potential compared to natural and designed FeCys4-containing proteins, we exploit it as terminal electron acceptor of a fully artificial chain triggered by visible light.