Carbonic anhydrase chemical models

Other reports concerning chemically modified amino acid as metal chelating agents used for the carbonic anhydrase active site model reconstruction are in close agreement with the small contribution of Zn(II) binding to the proton chemical shift variation discussed above. NMR experiments carried out in DMSO-rfg, at 300 K, and the observed... 

It is the intention of the authors to present a brief account on metal carbonato complexes which have a direct bearing on the reversible hydration of CO2 by the enzyme carbonic anhydrase. Emphasis is placed on the integration of the kinetic and mechanistic concepts derived from the studies on model systems with the available kinetic, chemical and structural information on the enzyme carbonic anhydrase. To start, the kinetics and equilibria of dissolved CO2, relevant to the present context, are presented. 

In natural processes, metal ions are often in high oxidation states (2 or 3), whereas in chemical systems the metals are in low oxidation states (0 or 1). This fact inverts the role of the metal center, such that it acts as a one-electron sink in a natural system, but as a nucleophile in an artificial ones (see other chapters of this book and the review by Aresta et al. [109]). Nevertheless, important biochemical processes such as the reversible enzymatic hydration of C02, or the formation of metal carbamates, may serve as natural models for many synthetic purposes. Starting from the properties of carbonic anhydrase (a zinc metalloenzyme that performs the activation of C02), Schenk et al. proposed a review [110] of perspectives to build biomimetic chemical catalysts by means of high-level DFT or ah initio calculations for both the gas phase and in the condensed state. The fixation of C02 by Zn(II) complexes to undergo the hydration of C02 (Figure 4.17) the use of Cr, Co, or Zn complexes as catalysts for the coordination-insertion reaction of C02 with epoxides and the theoretical aspects of carbamate synthesis, especially for the formation of Mg2+ and Li+ carbamates, are discussed in the review of Schenk... 

Figure 1 Refolding and aggregation model for bovine carbonic anhydrase B (CAB). When denatured CAB in 5 M GuHCl is rapidly diluted to refolding conditions, the unfolded protein, U, forms the first intermediate, 1 This intermediate continues to refold to the second intermediate, L, which proceeds to fold to the native protein, N. If the unfolded protein is diluted to aggregating conditions, the first intermediate will associate to form multimers. The dimer, D, and trimer, T, species can further associate, resulting in the formation of large aggregates. (Reproduced from ref. 1. Copyright 1990 American Chemical Society.)...

Khadikar, P.V., Sharma, V., Karmarkar, S. and Supuran, C.T (2005a) Novel use of chemical shift in NMR as molecular descriptor a first report on modeling carbonic anhydrase inhibitory activity and related parameters. Bioorg. Med. Chem. Lett., 15, 931-936. 

The chemical denaturant-dependent histidine hydrogen exchange protocol was initially developed and applied to several model protein systems including RNase A, myoglobin, and bovine carbonic anhydrase (BCA) II [32]. RNase A and myoglobin are known to have two-state folding behavior. BCA II is a non-two-state folding protein that is known to have a partially folded... 

---