Structural and functional aspects of copper transporting proteins

Abstract

The biogenic nature and esssentiality of copper in biological systems is well known. Due to both its oxidations–reduction activity and the intriguing coordination of chemistry, copper is most suited to play a vital role in cellular biochemistry. Hydrated copper ions themselves are highly reactive and would be in a position to interfere in many a biochemical pathway. For example, the Fenton Type generation of ·OH radicals would destroy the cellular architecture in an uncontrolled manner. Unwanted and non-specific binding of ionic copper to functional and/or structurally important biopolymers must be considered hazardous for living system. In electron transport and oxygen reduction the specific reaction of the bound copper is dictated by the macromolecular protein portion [1,2]. While some progress has been made on the structure-function correlation of some of these copper proteins little is known how the metal is implanted into these functionally important copper proteins. In order to avoid the uncontrolled reactivity of copper and to ascertain the proper insertion of this metal into a specific enzyme the need of an efficient transportation is obvious. At present only three copper-transporting proteins including the cupreins, caeruloplasmin and copper-thionein are fairly well characterized. The binding site of the cuprein copper has been elucidated by X-ray crystallography. The other two proteins have been chemically and spectroscopically studied, in the serum protein caeruloplasmin three different types of copper coordination are known while the copper chromophore in copperthionein appears to be homogeneous. Special emphasis will be placed on this thiolate rich copper protein. This type of copper binding protein appears to be very old origin. It is found in microorganisms as well as in animal cells. Its amino acid composition is even more simple compared to the amino acid residues found in the iron sulphur proteins. A striking phenomenon is the extraordinarily high cysteine content ranging up to 30%. In freshly isolated Cuthionein the copper is the cuprous state. Apart from the copper transportation in either protein some of these proteins display catalytic functions. For example, some of the copper in caerulophenoloxidase and is reported to function like a terminal cytochrome c oxidase. Furthermore, the function of a more or less specific iron oxidase has been suggested. The cupreins are discussed with great enthusiasm to catalyse the spontaneous superoxide dismutation. In the case of the copper-thioneins their role apparently remains to lie exclusively in metal transport.