Ribonuclease positively charged groups

Figuie 55. Stabilization of positively charged groups by bridging water molecules in the active site of native ribonuclease A without anions. The stereo drawing corresponds to a snapshot of the molecular dynamics trajectory at 15 ps. The picture includes only residues Lys-7, Arg-39, Lys-41, Lys-66, His-119, and the bound water molecules. The hydrogen-bonding criterion is the same as used in Fig. 54. 

The rate constant for reaction of the electron with biological polymers such as nucleic acids (11) and proteins (7) have been examined. When calculated on a per mole basis the rate constants can be quite high— e.g., ribonuclease (pH 6.8) k = 1.3 X 1010 M l sec.-1, lysozyme (pH 6.2) k = 7.5 X 1010 M l sec.""1), but they are much less than if the constituent units were in free solution. For ribonuclease an attempt has been made to estimate the rate constant from the rate constants for the constituent units (6). Allowance was made for the decrease in collision radius in going from the constituent units to the protein, and for the number of positive charges on the protein molecule. The estimated value agreed with the measured value to within a factor of two or three. If this approach is accepted, one can conclude that the strongest contribution to the reactivity arises from —SS groups, and this conclusion is in line with other evidence from radiation chemistry. 

Enzymes which catalyze the hydrolysis of the unit linkage of sequential residues of oligomers or polymers determine their substrate specificity by recognizing the particular unit residue in the sequential chain as well as the direction of the chain. For example, ribonuclease cleaves the 3 -phosphate of a pyrimidine nucleotide residue but not the 5 -phosphate, and trypsin hydrolyzes peptide bonds which involve the arginine or lysine residue at the carbonyl end but not at the amino end. This is also the case for the hydrolysis of a variety of synthetic substrates and quasi-substrates (Sect. 4.1). Synthetic trypsin substrates are ester or amide derivatives in which the site-specific group (positive charge) is contained in their carbonyl portion. 

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