Histidine hemocyanin ligand

Blue oxidases contain trinuclear centers, formally constructed of a single type 2 and a single type 3 copper center, in which the three copper ions form a triangle [25] (Fig. 8). Both copper ions of the type 3 copper center are coordinated by three histidines, while two histidines coordinate the type 2 copper ion [36,37]. In contrast to the type 3 copper centers of hemocyanin and tyrosinase, the ligands of the two copper ions are arranged prismatically [36, 39] as steric hindrance by the type 2 copper center prevents an antiprismatic arrangement. These trinuclear centers are one of the two known enzymatic structures able to reduce oxygen to water. 

The function of domain 1 has not yet been completely elucidated, although it may function as a medium of cooperative oxygen binding [37]. Domain 3 screens the copper center of domain 2 [237] from solvent. This copper center in domain 2 [34] is coordinated by six histidines from the helices 2.1 (2 His), 2.5 (2 His), 2.2 (1 His), and 2.6 (1 His). The histidine residue of helix 2.1 occurs in the sequence His-His-Trp-His-Trp-His, which is conserved in many arthropod hemocyanins. The histidines in helix 2.5 occur in the structure His-X-X-X-His. The coordination of two copper atoms with six ligands leaves two coordination sites free these two sites are utilized to bind oxygen [34],... 

The catalase-like action of hemocyanin is probably because of copper bound to one or more amino acids in the protein. Contrary to previous claims (12), arginine chelates with copper are not the only catalytically active species. For example, copper chelates with histidine and histamine are also active. The rates appear to be a first power function of copper and H202. Studies now being carried out with V. S. Sharma in our laboratories indicate that the active species is the Cu (II) L form where L represents the ligand. The copper chelate forms a ternary complex with... 

Although the sructure of tyrosinase is not known, evolutionary correlations 41), sequence homology 28), and spectroscopic similarities (6) with hemocyanin, particularly molluscan hemocyanin, and catechol oxidase indicate a common active site with six histidine ligands bound to the two copper ions. Thus, for instance, the electronic spectrum of oxy-tyrosinase exhibits... 

Most of the synthetic models we found in our literature survey are concerned with hemocyanine, the oxygen transport protein in arthropods and molluscs, and tyrosinase, which catalyzes the two-electron oxidation of phenolic compounds. Both proteins contain a coupled binuclear copper active site, a Type III copper centre,"which reversibly binds dioxygen as peroxide bridging between the two copper ions" [153]. The Cu-Cu distance is of the order of 300-400 pm, and a tetragonal coordination is achieved with donor nitrogen atoms of imidazole ligands from histidine [142]. 

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