Metalloproteins, active site

P2 The long-term goal of the proposed research is to create functional model complexes of metalloprotein active sites. (From Flouser, 2001)... 

Ru+2 complexes readily react with surface histidine residues to form stable derivatives. Photochemical methods were used to inject an electron into the Ru3+ site followed by monitoring kinetics of ET from Ru2+to the metalloprotein active site. 

Some information concerning the structures and functions of the metalloprotein active sites is required for any discussion of model complexes. Brief descriptions of the natural sites are therefore included and more detailed accounts may be found in the references. Where possible, references concerned with the metalloproteins themselves include recent reviews. 

A close relationship has existed between the field of bioinorganic chemistry and that of macrocyclic or macropolycyclic chemistry for the last 20 years. In part, this is due to direct overlap relating to the existence of the natural macrocyclic antibiotics and porphyrins. However, a long and fruitful association also exists in a third area the use of macrocyclic or cryptate complexes to model metalloprotein active sites or to mimic their chemistry (1-3). 

The metalloproteins that have attracted most attention are those whose properties are most obviously different from those observed in the normal classical aqueous coordination chemistry of the metal ions. The challenge is to account for (initially) unique spectral or chemical properties in terms of the coordination chemistry of the metalloprotein active site, as moderated by the protein environment. With increasing frequency, as in the case of type 1 copper (Section IIIB), crystallography reveals the active site structure with sufficient clarity to provide strong clues as to the origin of the unusual spectroscopy. However, an important test of the structural and spectroscopic analyses is to reproduce the same effects in a model complex. On other occasions, as with the [4Fe-4S] proteins (Section VC), many questions remained even after the structures were known. In spite of the very impressive achievements of protein crystallography, there remain many metalloproteins for which structural data are either not available or inconclusive. 

Fig. 1. Steps in the development of models for a metalloprotein active site.

Transition metal cofactors typically lose function when extracted from their host proteins. Related to this observation is the diminished, divergent, or nonexistent function of synthetic complexes modeled on metalloprotein active sites. Common to both of these phenomena is the loss of the tuning afforded by the protein matrix. The protein matrix surrounding such sites plays a vital role in the bioinorganic chemistry. 

The emergence of dimanganese units as potential metalloprotein active sites has resulted in an intense synthetic effort to model such sites. Since the metalloproteins are not structurally well characterized, there are few... 

R 297 B. Bennett, EPR of Co(II) as a Structural and Mechanistic Probe of Metalloprotein Active Sites Characterisation of an Aminopeptidase , Curr.Top.Biophys., 2002,26,49... 

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