Protein structure and reactivity

Jackson, J. C., Hammill, J. T. and Mehl, R. A. (2007) Site-specific incorporation of a F-19-amino acid into proteins as an NMR probe for characterizing protein structure and reactivity. Journal of the American Chemical Society, 129(5), 1160-1166. 

When discussing various methods for the synthesis of protein-like HP-copolymers from the monomeric precursors (Sect. 2.1), we pointed to the possibility of implementation of both polymerization and polycondensation processes. The studies of the potentials of the latter approach in the creation of protein-like macromolecular systems have already been started. The first published results show that using true selected reactions of the polycondensation type and appropriate synthetic conditions (structure and reactivity of comonomers, solvent, temperature, reagent concentration and comonomer ratio, the order of the reagents introduction into the feed, etc.) one has a chance to produce the polymer chains with a desirable set of monomer sequences. 

Fletcher PDl, Parrot D (1989) Protein-partitioning between water-in-oil microemulsions and conjugate aqueous phases. In Pileni MP (ed) Structure and reactivity in reverse micelles. Elsevier, Amsterdam, p 303... 

Our own work in the area of aerobic oxidations was inspired by the exquisite research performed on the structure and reactivity of the binuclear copper proteins (7), hemocyanin and tyrosinase, and by the seminal contribution of Riviere and Jallabert (8). These two authors have shown that the simple copper complex CuCl - Phen (Phen = 1,10-phenanthroline) promoted the aerobic oxidation of benzylic alcohols to the corresponding aromatic aldehydes and ketones (Fig. 2). 

This chapter focuses on the chemistry ofbiomimetic copper nitrosyl complexes relevant to the NO-copper interactions in proteins that are central players in dissimilatory nitrogen oxide reduction (denitrification). The current state of knowledge of NO-copper interactions in nitrite reductase, a key denitrifying enzyme, is briefly surveyed the syntheses, structures, and reactivity of copper nitrosyl model complexes prepared to date are presented and the insight these model studies provide into the mechanisms of denitrification and the structures of other copper protein nitrosyl intermediates are discussed. Emphasis is placed on analysis of the geometric features, electronic structures, and biomimetic reactivity with NO or NOf of the only structurally characterized copper nitrosyls, a dicopper(II) complex bridged by NO and a mononuclear tris(pyrazolyl)hydroborate complex having a Cu(I)-NO formulation. 

The dioxygen-carrying proteins, hemoglobin and myoglobin, as well as the many synthetic model systems that have been developed recently,44 will not be considered here in this chapter since their chemistry is mainly that of iron in the + 2 oxidation state. The present chapter is therefore restricted to a brief description of the structure and reactivity of some cytochrome and peroxidase proteins. 

There was no similar correlation between reactivity toward Fe(ll) and solvent exposure. FetSp and hCp exhibited similar rates of type 1 Cu(ll) reduction by Fe(ll) kohs > 1200s" ) while the rate with Co. cinereus Lac was >23s . In other words, laccases can use Fe(ll) as substrate but have no better than 1-2% of this activity in comparison to FetSp and hCp. In addition, they are at least 100-fold better than the ferroxidases in the turnover of bulky organic reductants. Combining the structure and reactivity features of these proteins indicates that the type 1 sites in the ferroxidases are less accessible to these large reductants and at the same time possess specificity elements that support the recognition and binding of Fe(II) as substrate. As outlined above, some of these elements may have been identified in hCp they remain uncharacterized in FetSp. 

The synthesis, structures, and reactivities of metal thiolates with group 4 and 5 metals, and the synthesis and study of copper-thiolates have been reviewed. Hg thiolate chemistry has been reviewed and related to the binding of Hg in vivo by metalloregulatory proteins. A range of two-, three-, and four-coordinate Hg thiolate complexes has been prepared, and comparisons with the metalloregulatory protein, Hg-MerR,... 

In vitro, both metals in the active site of SOD can be reversibly removed. This behavior has been elegantly expanded to produce a variety of metal-substituted derivatives. Co, Ni, and Ag derivatives, where the added metal ion may occupy the copper site or the zinc site (and in some cases both), have proven especially valuable in providing new spectroscopic probes of metal-site structure and reactivity in Cu, Zn SOD. Application of in vitro metal substitution to several of the FALS wild-type-like mutants has shown that these variants readily misfold and often exhibit altered metal ion binding. In addition to the in vitro metal studies, recent work has centered on the mechanism of in vivo copper incorporation. CCS is a copper chaperone protein that forms a heterodimer with Zn-loaded SOD to insert copper and activate the enzyme (see Metallochaperones Metal Ion Homeostasis). 

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