RNase A: Difference between revisions

Due to the high rate of RNA hydrolysis by RNase A, mammalian cells have developed a protective inhibitor to prevent pancreatic ribonucleases from degrading cystolic RNA. Ribonuclease Inhibitor (RI) tightly associates to the active site of RNase A due to its <scene name='User:R._Jeremy_Johnson/RNaseA/Ri_simple/1'>non-globular nature</scene>. RI is a 50 kD protein that is composed of 16 repeating subunits of alpha helices and beta sheets, giving it a noticeable <scene name='User:R._Jeremy_Johnson/RNaseA/Ri_nonglobular/1'>horseshoe like appearance</scene>. The RI-RNase protein-protein interaction has the highest known affinity of any protein-protein interactions with an approximate dissociation constant (''K''d) of 5.8 X 10-14 for almost all types of ribonucleases.<ref>PMID:7877692</ref> The ability to be selective for almost all types of RNases, and yet retain such a high Kd is product of its mechanism of inhibition. The interior residues of the horseshoe shaped RI are able to bind to the charged residues of the active site cleft of RNase A, such as <scene name='User:R._Jeremy_Johnson/RNaseA/Ri_rnasea_lys7_gln11_lys41/1'>Lys7, Gln11, and Lys41 </scene>. By studying the amphibian RNase, Onconase, the residues Lys7 and Gln11 of RNase A were shown to be the most important in this interaction. In onconase, these residues are replaced with non-charged amino acids, which help prevent the binding of RI to the protein <ref>PMID:18930025</ref>