The nature of the allosteric interactions of ribonuclease and its ligands

Abstract

The allosteric model for ribonuclease activity proposed by Walker, Ralston & Darvey [(1975) Biochem. J. 147, 425-433; (1976) Biochem. J. 153, 329-337] involves the binding of a large number of molecules of substrate or substrate analogue to a series of allosteric sites on the enzyme. In the present paper, the nature of these allosteric interactions is investigated. The effects of ionic strength, pH, carbamoylation of lysine to homocitrulline and of deamidation of glutamine and asparagine on plots of velocity versus substrate concentration are examined and evidence is presented that the allosteric transition involves an electrostatic interaction between the negatively charged substrate molecules and the cationic groups on the enzyme.

Positional preferences in flavonoids for inhibition of ribonuclease A: Where “OH” where?

“…From the docking studies, we have seen that the ligands bind in close proximity of helix 3‐13 and helix 24‐33 of RNase as well as those involved in phosphate binding. The binding site for the flavonoids as determined by the docking studies is at the established peripheral binding site for RNA in RNase A 56‐58 . This is further supported by non‐competitive inhibition displayed by some of the flavonoids.…”