Structure of the hydrophobic core in the transition state for folding of chymotrypsin inhibitor 2: A critical test of the protein engineering method of analysis

Biochemistry ◽  
1993 ◽  
Vol 32 (42) ◽  
pp. 11270-11278 ◽  
Author(s):  
Sophie E. Jackson ◽  
Nadia elMasry ◽  
Alan R. Fersht
Keyword(s):  
Protein Engineering ◽  
Transition State ◽  
Engineering Method ◽  
Hydrophobic Core ◽  
Critical Test ◽  
Chymotrypsin Inhibitor ◽  
Chymotrypsin Inhibitor 2

Mapping the structures of transition states and intermediates in folding: delineation of pathways at high resolution

1995 ◽  
Vol 348 (1323) ◽  
pp. 11-15 ◽  
Keyword(s):  
Secondary Structure ◽  
Protein Engineering ◽  
Transition State ◽  
Transition States ◽  
Native Structure ◽  
Denatured State ◽  
Chymotrypsin Inhibitor 2 ◽  
Rate Determining Step ◽  
Framework Model ◽  
Individual Domain

The structures of all the intermediates and transition states, from the unfolded state to the native structure, are being determined at the level of individual residues in the folding pathways of barnase and chymotrypsin inhibitor 2 (CI2), using a combination of protein engineering and nuclear magnetic resonance methods. Barnase appears to refold according to a classical framework model in which elements of secondary structure are flickeringly present in the denatured state, consolidate as the reaction proceeds and, when nearly fully formed, dock in the rate-determining step. Unlike barnase, CI2 folds without a kinetically significant folding intermediate. The transition state for its formation has no fully formed elements of secondary structure, and the transition state is like an expanded form of the native structure. CI2 probably represents the folding of an individual domain in a larger protein, whereas barnase represents the folding of a multi-domain protein. The protein engineering methods are being extended to map the pathway in the presence of molecular chaperones. There are parallels between the folding of barnase when bound to GroEL and in solution.

Effect of cavity-creating mutations in the hydrophobic core of chymotrypsin inhibitor 2

Biochemistry ◽  
1993 ◽  
Vol 32 (42) ◽  
pp. 11259-11269 ◽  
Author(s):  
Sophie E. Jackson ◽  
Marco Moracci ◽  
Nadia elMasry ◽  
Christopher M. Johnson ◽  
Alan R. Fersht
Keyword(s):  
Hydrophobic Core ◽  
Chymotrypsin Inhibitor ◽  
Chymotrypsin Inhibitor 2
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