Ribonuclease inhibitor (RI) is a cytoplasmic protein of ∼50 kDa that tightly binds and inhibits ribonucleases (RNases) from the pancreatic superfamily (1 ). Diverse RNases with very limited sequence similarities, including RNase A, angiogenin, RNase-2 (also known as eosinophil-derived neurotoxin (EDN) or placental RNase), and RNase-4 are inhibited withKi values between 10−14 and 10−16M. These affinities are among the highest reported for noncovalent binding of proteins. The binding occurs with 1∶1 stoichiometry. A subset of the pancreatic ribonuclease superfamily, including the amphibian ribonucleases such as frog-liver ribonuclease, sialic acid-binding lectin, and P-30 protein, are not inhibited by RI. The potent inhibitory activity of RI is believed to be utilized in RNA processing, angiogenesis, and protection of the cell from toxic ribonucleases.
