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Summary: letters
394 nature structural biology · volume 7 number 5 · may 2000
Two energetically disparate
folding pathways of -lytic
protease share a single
transition state
Alan I. Derman and David A. Agard
The Howard Hughes Medical Institute and the Department of Biochemistry
and Biophysics, University of California, San Francisco, 513 Parnassus
Avenue, Box 0448, San Francisco, California 94143-0448, USA.
The Lysobacter enzymogenes -lytic protease (LP) is syn-
thesized with a 166 amino acid pro region (Pro) that catalyzes
the folding of the 198 amino acid protease into its native con-
formation. An extraordinary feature of this system is the very
high energy barrier (G = 30 kcal mol-1) that effectively pre-
vents LP from folding in the absence of Pro (t1/2 = 1800
years). A pair of mutations has been isolated in the protease
that completely suppresses the catalytic defect incurred in
Pro by truncation of its last three amino acids. These muta-
tions also accelerate the folding of LP in the absence of Pro
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