Enzyme active sites, nonpolar

Exercise 9.1. Evaluate the energetics of the reaction of Fig. 9.2 in a nonpolar enzyme-active site. 

Enzyme active sites, 136,148, 225. See also Protein active sites in carbonic anhydrase, 197-199 in chymotrypsin, 173 in lysozyme, 153, 157 nonpolar (hypothetical site), 211-214 SNase, 189-190,190 steric forces in, 155-158, 209-211, 225 in subtilisin, 173 viewed as super solvents, 227 Enzyme cofactors calcium ... 

THE DESOLVATION PROPOSAL AND THE ASSUMPTION THAT ENZYME ACTIVE SITES ARE NONPOLAR... 

As in the case of pyridoxal phosphate, the key to reaction in this case is the use of a heterocyclic compound as an electron sink in the decarboxylation step. Conformational control of the TPP-pyruvate adduct may also be important. The enzyme active site is probably nonpolar, and this provides a significant catalytic factor (112). 

Synthetic molecular receptors command widespread interest as mimics of membrane transport agents and enzyme active sites.[1,2] The development of new host systems for the selective complexation of organic and inorganic cations and anions has mushroomed in recent years however, examples of solution phase coordination of neutral organic molecules are few. Most of these examples involve inclusion of an aromatic hydrocarbon into the hydrophobic pocket of a water soluble cyclodextrin or cyclophane receptor.[3-6] A smaller subset of synthetic receptors possess lipophilic exteriors and hydrophilic cavities for the association of polar substrates in nonpolar media. [7-9] We report here the synthesis and characterization of a new system of the latter type designed to bind polar guests in chloroform solution. 

This calculation demonstrates that a nonpolar solvent can accelerate S 2 reactions. However, this is not what we are asking the relevant quantity is the overall activation energy for the reaction in a nonpolar enzyme which is surrounded by water. Thus, as is indicated in the thermodynamic cycle of Fig. 9.3, we should include the energy of moving the ionized R-O- from water to the nonpolar active site (AAg j1). Thus the actual apparent change in activation barrier is... 

The active site is in a cleft between a large domain with a nonpolar core and a smaller (3-sheet domain that contains many hydrogen-bonded polar side chains (Figs. 12-3,12-4). Human lysozyme has a similar structure and properties.57-59 The T4 lysozyme has an additional C-terminal domain whose function may be to bind the crosslinking peptide of the E. coli peptidoglycan. Goose lysozyme is similar in part to both hen lysozyme and T4 lysozyme. All three enzymes, as well as that of our own tears, may have evolved from a common ancestral protein.60 On the other hand, Streptomyces erythaeus has developed its own lysozyme with a completely different structure.61 An extensive series of T4 lysozyme mutants have been studied in efforts to understand protein folding and stability.61-63... 

In both carboxypeptidase A and thermolysin the active site Zn2+ is chelated by two imidazole groups and a glutamate side chain (Fig. 12-16). In carboxypeptidase A, Arg 145, Tyr 248, and perhaps Arg 127 form hydrogen bonds to the substrate. A water molecule is also bound to the Zn2+ ion. The presence of the positively charged side chain of Arg 145 and of a hydro-phobic pocket accounts for the preference of the enzyme for C-terminal amino acids with bulky, nonpolar side chains. The Zn2+ in thermolysin is also bound to two imidazole groups and that in D-alanyl-D-alanyl carboxypeptidase to three. 

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