Implications for enzymic catalysis

The study of both carbonyl and carbon acid participation in ester hydrolysis has been used by Bowden and Last (1971) to evaluate certain of the factors suggested for important roles in enzymic catalysis. A first model concerns a comparison of the three formyl esters and shows that the proximity of the formyl to the ester group and internal strain increase in passing along the series, 1,2-benzoate, 1,8-naphthoate and 4,5-phenanthroate. The very large rate enhancements result from the proximity of the internal nucleophile once formed and from internal strain. Strain is increased or induced by the primary 

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S. J., Klinman, J. P. (1996) Experimental evidence for extensive tunneling of hydrogen in the lipoxygenase reaction - implications for enzyme catalysis, J. Am. Chem. 

Guo, H. and Salahub, D.R. (2001) Origin of the high basicity of 2,7-dimethoxy-l,8-bis (dimethylamino)naphthalene implications for enzyme catalysis. Journal of Molecular Structure (Theochem), 547, 113—118. 

B. Schwartz and D.G. Drucckhammer, A simple method for determining the relative strengths of normal and low-barrier hydrogen bonds in solution Implications to enzyme catalysis, J. Am. Chem. Soc., 117 (1995) 11902. 

The considerable detail to which we now can understand enzyme catalysis is well illustrated by what is known about the action of carboxypeptidase A. This enzyme (Section 25-7B and Table 25-3) is one of the digestive enzymes of the pancreas that specifically hydrolyze peptide bonds at the C-terminal end. Both the amino-acid sequence and the three-dimensional structure of carboxypeptidase A are known. The enzyme is a single chain of 307 amino-acid residues. The chain has regions where it is associated as an a helix and others where it is associated as a /3-pIeated sheet. The prosthetic group is a zinc ion bound to three specific amino acids and one water molecule near the surface of the molecule. The amino acids bound to zinc are His 69, His 196, and Glu 72 the numbering refers to the position of the amino acid along the chain, with the amino acid at the /V-terminus being number l. The zinc ion is essential for the activity of the enzyme and is implicated, therefore, as part of the active site. 

Experiments have shown that a metal is required for catalysis to occur but activity is seen for metals other than zinc. Its activity is inhibited by other small molecules that can bind to zinc in place of water and carbon dioxide, in particular cyanide, hydrogen sulfide and chloride that all bind tenaciously to transition metals. As well as its buffering ability, this enzyme represents a valuable method of converting carbon dioxide into carbonate so any advances in mimicking the behaviour of this enzyme may have implications for carbon storage. Conceivably carbon dioxide could be passed through a vat containing an aqueous solution of a carbonic... 

What are the possible functional implications of such gating motions Ensuring the maximum possible speed of binding is clearly one function. For example, it is necessary to create a special environment around a substrate for enzymatic catalysis, but evolutionary pressure has forced the creation of this environment to happen very rapidly for certain enzymes. 

Sigel RKO, Pyle AM Alternative roles for metal ions in enzyme catalysis and the implications for ribozyme chemistry. Chem Rev 2007, 107(1) 97-113. 

In addition to the active serine-195 residue, the other active site residues are histidine-57 and aspartic add-102, deduced from the X-ray work. The other histidine residue, His-40, is not implicated in the catalysis. The enzyme has a specificity for aromatic amino acids. Esters of aromatic amino adds are also good substrates for the enzyme and most of the kinetic data were obtained with ester substrates. The enzyme cuts up proteins on the carboxyl side of aromatic amino acids. After the formation of the Michaelis complex the uniquely reactive Ser-195 is first acylated to form an acyl-enzyme intermediate with the substrate. 

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