Structural Determinants of Limited Proteolysis

• DOI: 10.1021/pr200271w
• Publication Date: 2011-06-18T02:02:27Z
• Authors: Marat D. Kazanov; Yoshinobu Igarashi; Alexey M. Eroshkin; Piotr Cieplak; Boris Ratnikov; Ying Zhang; Zhanwen Li; Adam Godzik; Andrei L. Osterman; Jeffrey W. Smith
• Keywords: Proteolysis

Limited or regulatory proteolysis plays a critical role in many important biological pathways like blood coagulation, cell proliferation, and apoptosis. A better understanding of mechanisms that control this process is required for discovering new proteolytic events developing inhibitors with potential therapeutic value. Two features determine the susceptibility peptide bonds to are sequence vicinity scissile bond structural context which displayed. In study, we assessed statistical significance predictive power individual descriptors combination thereof identification cleavage sites. The analysis was performed on data set >200 documented CutDB variety mammalian proteases their physiological substrates known 3D structures. results confirmed provided ranking within three main categories features: exposure > flexibility local interactions. Among secondary structure elements, largest frequency loops lower but significant helices. has albeit appreciable occurrence certain types β-strands, contrast some previous reports. Descriptors deduced directly from amino acid displayed only marginal capabilities. Homology-based models showed performance comparable protein experimentally established Overall, study foundation accurate automated prediction segments susceptible processing and, potentially, other post-translational modifications.