Three-dimensional structure of human RNase 1 Delta N7 at 1.9 angstrom resolution

Human pancreatic ribonuclease 1 (RNase 1) is considered to be the human cou nterpart of bovine pancreatic RNase A. Truncation of seven amino-acid resid ues from the aminoterminal sequence resulted in RNase 1 Delta N7, which has a reduced ribonucleolytic activity and a lower affinity for the human plac ental RNase inhibitor (PRI). This RNase 1 variant has been cloned, heterolo gously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data to 1.9 Angstrom resolution. The mole cule displays the alpha + beta folding topology typical of members of the R Nase A superfamily. The main distinct features found in RNase 1 Delta N7 ar e basically located in three loops affecting the fitting of the enzyme to t he active site of subtilisin and the shape of the B2 subsite. These changes , taken with the lack of the catalytically active residue Lys7, may explain the reduced affinity of RNase 1 Delta N7 for PRI and the low ribonucleolyt ic activity of the protein when compared with the native enzyme.