Tyrosinases, bifunctional metalloenzymes, catalyze the oxidation of monophenols ando-diphenols too-quinones, the precursor compounds of the brown-coloured pigment melanin. In eukaryotic organisms, tyrosinases are expressed as latent zymogens that have to be proteolytically cleaved in order to form highly active enzymes. This activation mechanism, known as the tyrosinase maturation process, has scientific and industrial significance with respect to biochemical and technical applications of the enzyme. Here, not only the first crystal structure of the mushroom tyrosinaseabPPO4 is presented in its active form (Ser2–Ser383) and in its 21 kDa heavier latent form (Ser2–Thr545), but furthermore the simultaneous presence of both forms within one single-crystal structure is shown. This allows for a simple approach to investigate the transition between these two forms. IsoformabPPO4 was isolated and extensively purified from the natural source (Agaricus bisporus), which contains a total of six polyphenol oxidases (PPOs). The enzyme formed crystals (diffracting to a resolution of 2.76 Å) owing to the employment of the 6-tungstotellurate(VI) salt (Na₆[TeW₆O₂₄]·22H₂O) as a cocrystallization agent. Two of these disc-shaped Anderson-type polyoxoanions [TeW₆O₂₄]⁶⁻separate two asymmetric units comprising one crystallographic heterodimer ofabPPO4, thus resulting in very interesting crystal packing.

As synchrotron radiation becomes more intense, detectors become faster and structure‐solving software becomes more elaborate, obtaining single crystals suitable for data collection is now the bottleneck in macromolecular crystallography. Hence, there is a need for novel and advanced crystallisation agents with the ability to crystallise proteins that are otherwise challenging. Here, an Anderson–Evans‐type polyoxometalate (POM), specifically Na₆[TeW₆O₂₄]⋅22 H₂O (TEW), is employed as a crystallisation additive. Its effects on protein crystallisation are demonstrated with hen egg‐white lysozyme (HEWL), which co‐crystallises with TEW in the vicinity (or within) the liquid–liquid phase separation (LLPS) region. The X‐ray structure (PDB ID: 4PHI) determination revealed that TEW molecules are part of the crystal lattice, thus demonstrating specific binding to HEWL with electrostatic interactions and hydrogen bonds. The negatively charged TEW polyoxotungstate binds to sites with a positive electrostatic potential located between two (or more) symmetry‐related protein chains. Thus, TEW facilitates the formation of protein–protein interfaces of otherwise repulsive surfaces, and thereby the realisation of a stable crystal lattice. In addition to retaining the isomorphicity of the protein structure, the anomalous scattering of the POMs was used for macromolecular phasing. The results suggest that hexatungstotellurate(VI) has great potential as a crystallisation additive to promote both protein crystallisation and structure elucidation.