Binding Metalloproteins

Interactions and Functions of some Calcium-Binding Proteins 

Aequorin Bioluminescent protein which emits light on binding Ca2+ (346) has been used as a fluorescent chelator to monitor Ca2+ concentrations. 

Annexins Phospholipid- and membrane-binding proteins involved in the regulation of cell growth, coagulation, mediation of secretion, signal transduction, and ion channel activity link signaling to membrane dynamics 

Ca2+-ATPase (348,349) Provides the means of pumping Ca2+ selectively across membranes (350,351) 

Cadherins Transmembrane glycoproteins (352) promoting cellcell adhesion (353,354) linked to integrins (355) and via catenins to muscle action (356) 

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These are only a few examples indicating the scope of this emerging area of research at the interface of peptide and protein chemistry and coordination chemistry. The synthesis of metal-binding metalloproteins and the introduction of redox-active metal centers into artificial proteins by self-assembly processes is surely only the beginning. One can certainly think of extending this approach to the incorporation of substrate-binding enzymatic func-... 

Fritz G, Heizmann CW (2004) 3D-structures of the Ca2+-and Zn2+-binding SI00 proteins. In Messerschmidt A, Bode W, Cygler M, Handbook of metalloproteins. Wiley, Chichester, pp, 529—540... 

The fact that imidazole (Him) residues are particularly popular transition metal binding sites within metalloproteins is a major driving force for investigations of this heterocycle. The divalent... 

Numbers of Calcium-Binding Sites in Selected Metalloproteins... 

Metal chelate affinity chromatography finds most prominent application in the affinity purification of recombinant proteins to which a histidine tag has been attached (described later). As protein binding occurs via the histidine residues, this technique is no more inherently useful for the purification of metalloproteins than for the purification of non-metalloproteins (a common misconception, given its name). 

Metallothionein was first discovered in 1957 as a cadmium-binding cysteine-rich protein (481). Since then the metallothionein proteins (MTs) have become a superfamily characterized as low molecular weight (6-7 kDa) and cysteine rich (20 residues) polypeptides. Mammalian MTs can be divided into three subgroups, MT-I, MT-II, and MT-III (482, 483, 491). The biological functions of MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis, and regulation of the biosynthesis and activity of zinc metalloproteins. 

The normal cellular form of prion protein (PrPc) can exist as a Cu-metalloprotein in vivo (492). This PrPc is a precursor of the pathogenic protease-resistant form PrPsc, which is thought to cause scrapie, bovine spongiform encephalopathy (BSE), and Creutzfeldt—Jakob disease. Two octa-repeats of PHGGGWGQ have been proposed as Cu(II) binding sites centered on histidine (493). They lack secondary and tertiary structure in the absence of Cu(II). Neurons may therefore have special mechanisms to regulate the distribution of copper. 

In addition to the amino acid side chains mentioned above, a number of other low molecular weight ligands are found in metalloproteins. These include cyanide and carbon monoxide, which we will describe later in this chapter. Here we consider carbonate and phosphate anions in the context of the super family of iron-binding proteins, the transferrins. 

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