Matrix metalloprotein

Elkington PT, O Kane CM, Friedland JS. The paradox of matrix metalloprotein-ases in infectious disease. Clin Exp Immunol 2005 142(1) 12-20. 

At least 64 different matrix metalloproteins are known.427 Each enzyme consists of three domains. 

The ability to exist in more than one oxidation state allows transition-metal complexes to serve as the active site of enzymes whose function is to transfer electrons (39). A great deal of effort has been directed at understanding the mechanisms of electron transfer in metalloproteins, such as cytochromes and blue copper proteins (40). Of particular interest is the mechanism by which an electron can tunnel from a metal center that is imbedded in a protein matrix to a site on the outer surface of the protein (7). A discussion of current theories is given in this volume. 

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 interaction between the protein matrix and its nested coordination complexes is exemplary of outer sphere coordination (OSC). Recently, OSC has guided the design of both small molecules and metalloproteins to tune existing or imbue novel properties. While often cited to explain metalloprotein behavior, OSC is not typically treated in a descriptive manner. We will begin with Bjerrum s favored definition [1] of coordination in the second sphere (chosen from Werner s original postulation [2]) a complex with a fully occupied first sphere has residual affinity to attach groups. This mode of OSC is involved in supramo-lecular chemistry [3, 4], but does not quite suit our present discussion. 

Holm et al. have referred to metalloproteins as elaborated inorganic complexes, and it is computationally and conceptually useful to consider the immediate environment of a transition metal in a protein active site as a coordination complex surrounded by an unusual solventlike environment provided by the folded polypeptide of the protein. In many cases, redox active metal binding sites are sufficiently embedded in the protein matrix such that the actual solvent (water and/or lipid membranes) may have little impact on the redox thermochemistry of the site. Specific features of the active site beyond the first coordination shell (e.g., hydrogen bonds, charged peptide side chains) can have a significant impact on the redox properties of the site. Spectroscopic probes based on the properties of the metal reporter can then provide detailed information about the bonding and electronic structure of the redox active site. Thus, rather spatially limited theoretical calculations on redox active metal sites can be used to complement and interpret experimental data. 

The information on the chemical speciation of trace elements in biological systems is much needed to evaluate their biological significance. Although a number of analytical techniques based on atomic behavior are available for the analysis of chemical speciation of trace elements, neutron activation analysis, as a nuclear analytical technique, can be successfully used in chemical speciation studies, after appropriate fractionation steps. Table 2.5 lists some typical applications of NAA in chemical speciation analysis of metalloproteins. The main advantages of NAA are of its high sensitivity and the absence of matrix effects inherited from the conventional neutron activation analysis. It can, therefore, be used to analyze the chemical species of trace elements in very small samples or complicated matrices, which is often impossible for non-nuclear techniques. 

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