TY - JOUR
T1 - Folding mediated by an intramolecular chaperone
T2 - Autoprocessing pathway of the precursor resolved via a substrate assisted catalysis mechanism
AU - Shinde, Ujwal
AU - Inouye, Masayori
N1 - Funding Information:
We thank Dr Ann Stock and Dr Barbara Brodsky, Dr Parkash Badola and Jan Yadav for their helpful discussions during this entire work. The present work is partially supported by a grant from Ajinomoto Co. Ltd. and the National Science Foundation grant number MCB 9105293.
PY - 1995
Y1 - 1995
N2 - Subtilisin is synthesized with an N-terminal propeptide which has been demonstrated to function as an intramolecular chaperone that is only essential for the folding of the active enzyme. After folding, the propeptide is removed via an intramolecular autoprocessing mechanism. This mechanism is blocked when His64, a member of the catalytic triad is substituted with Ala. However, an additional mutation in the propeptide substituting Glu-2 with His was able to suppress the His64Ala mutation, allowing autoprocessing of the propeptide. This suppression is considered to be due to a 'substrate assisted catalysis' mechanism and demonstrates that the cleavage to the subtilisin propeptide is an autocatalytic process.
AB - Subtilisin is synthesized with an N-terminal propeptide which has been demonstrated to function as an intramolecular chaperone that is only essential for the folding of the active enzyme. After folding, the propeptide is removed via an intramolecular autoprocessing mechanism. This mechanism is blocked when His64, a member of the catalytic triad is substituted with Ala. However, an additional mutation in the propeptide substituting Glu-2 with His was able to suppress the His64Ala mutation, allowing autoprocessing of the propeptide. This suppression is considered to be due to a 'substrate assisted catalysis' mechanism and demonstrates that the cleavage to the subtilisin propeptide is an autocatalytic process.
KW - Autoprocessing mechanism
KW - Intramolecular chaperone
KW - Propeptide
KW - Protein folding
KW - Substrate assisted catalysis
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U2 - 10.1006/jmbi.1994.0147
DO - 10.1006/jmbi.1994.0147
M3 - Article
C2 - 7714895
AN - SCOPUS:0028949981
SN - 0022-2836
VL - 247
SP - 390
EP - 395
JO - Journal of molecular biology
JF - Journal of molecular biology
IS - 3
ER -