2010 Fiscal Year Final Research Report

Autoprocessing mechanism of SARS-CoV 3CL protease

Research Project

Project/Area Number	20570115
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Structural biochemistry
Research Institution	The Institute of Physical and Chemical Research
Principal Investigator	MURAMATSU Tomonari The Institute of Physical and Chemical Research, システム研究チーム, 上級研究員 (70212256)
Project Period (FY)	2008 – 2010
Keywords	SARS / プロテアーゼ / プロセシング / 基質認識 / 基質特異性 / 立体構造
Research Abstract	3C like protease (3CLPro) of severe acute respiratory syndrome coronavirus (SARS-CoV) is synthesized as a part of polyprotein, and is excised by its own proteolytic activity. It has been previously reported that the precise processing of N-terminus of 3CLPro is required for efficient peptidase activity toward the florogenic peptide substrate. However, by the use of an E. coli in vitro protein synthesis system, we found that the C-terminal site of 3CLPro was efficiently cleaved even though N-terminal pro-sequence was not removed. Moreover, the substrate specificity of this autoprocessing activity was different from that of the mature enzyme. We also found the pocket for this special recognition by X-ray crystallography.