Core Function

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Science  23 Mar 2012:
Vol. 335, Issue 6075, pp. 1410
DOI: 10.1126/science.335.6075.1410-c

Numerous metalloenzymes make use of their metal centers to promote substrate oxidations in a highly controlled fashion. Chemists have long wondered in this context how much of the reactivity is intrinsic to the local coordination environment of the active site, and how much relies on the extended scaffolding of the surrounding protein. Citek et al. now show that in the particular case of tyrosinase—an enzyme that oxidizes phenols in the service of melanin biosynthesis—a bimetallic complex that essentially constitutes the bare active site manifests its central reactivity pattern at low temperature. In the enzyme, two copper ions, each held in place by three imidazole rings tethered to histidines, bind oxygen via a bridging side-on coordination motif. The authors find that combining a copper salt, imidazole, and oxygen in solution at −125°C in arbitrary order leads directly to assembly of a complex that mimics the active site structurally (based on x-ray, ultraviolet, and optical absorption spectroscopy) and functionally (based on the relative kinetics of reactions with phenols of varying electronic properties). The complex falls apart as the temperature goes up, suggesting that the primary role of the protein in this case is to keep the naturally reactive coordination sphere intact and inhibit destructive side reactions.

Nat. Chem. 4, 10.1038/NCHEM.1284 (2012).

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