Application of physical organic chemistry to engineered mutants of proteins: Hammond postulate behavior in the transition state of protein folding.
Transition states in protein folding may be analyzed by linear free-energy relationships (LFERs) analogous to the Brønsted equation for changes in reactivity with changes in structure. There is an additional source of LFERs in protein folding: the perturbation of the equilibrium and rate constants by denaturants. These LFERs give a measure of the position of the transition state along the reaction coordinate. The transition state for folding/unfolding of barnase has been analyzed by both types of LFERs: changing the structure by protein engineering and perturbation by denaturants. The combination has allowed the direct monitoring of Hammond postulate behavior of the transition state on the reaction pathway. Movement of the transition state has been found and analyzed to give further details of the order of events in protein folding.
Matouschek
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A
Cambridge Centre for Protein Engineering, University Chemical Laboratory, United Kingdom.
Fersht
A R
AR
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002151:Calorimetry; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
D001426:Bacterial Proteins; D011506:Proteins; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease