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Disabling the folding catalyst is the last critical step in -lytic protease folding
 

Summary: Disabling the folding catalyst is the last critical step
in -lytic protease folding
ERIN L. CUNNINGHAM1
AND DAVID A. AGARD2,3
1
Graduate Group in Biophysics, 2
Howard Hughes Medical Institute, and 3
Department of Biochemistry and
Biophysics, University of California at San Francisco, San Francisco, California 94143-2240, USA
(RECEIVED August 21, 2003; FINAL REVISION October 15, 2003; ACCEPTED October 16, 2003)
Abstract
Alpha-Lytic protease ( LP) is an extracellular bacterial pro-protease marked by extraordinary conforma-
tional rigidity and a highly cooperative barrier to unfolding. Although these properties successfully limit its
proteolytic destruction, thereby extending the functional lifetime of the protease, they come at the expense
of foldability (t1/2 1800 yr) and thermodynamic stability (native LP is less stable than the unfolded
species). Efficient folding has required the coevolution of a large N-terminal pro region (Pro) that rapidly
catalyzes LP folding (t1/2 23 sec) and shifts the thermodynamic equilibrium in favor of folded protease
through tight native-state binding. Release of active LP from this stabilizing, but strongly inhibitory,
complex requires the proteolytic destruction of Pro. LP is capable of initiating Pro degradation via cleavage
of a flexible loop within the Pro C-terminal domain. This single cleavage event abolishes Pro catalysis while

  

Source: Agard, David - Department of Biochemistry and Biophysics, University of California at San Francisco

 

Collections: Biotechnology; Biology and Medicine