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Protein Engineering, Vol. 12, No. 1, 41-45, January 1999
© 1999 Oxford University Press

Analysis of protein–protein interactions by mutagenesis: direct versus indirect effects

Daniel E. Otzen1 and Alan R. Fersht2

MRC Unit for Protein Function & Design, Cambridge IRC for Protein Engineering, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK

Site-directed mutagenesis, including double-mutant cycles, is used routinely for studying protein–protein interactions. We now present a case analysis of chymotrypsin inhibitor 2 (CI2) and subtilisin BPN' using (i) a residue in CI2 that is known to interact directly with subtilisin (Tyr42) and (ii) two CI2 residues that do not have direct contacts with subtilisin (Arg46 and Arg48). We find that there are similar changes in binding energy on mutation of these two sets of residues. It can thus be difficult to interpret mutagenesis data in the absence of structural information.

Keywords: chymotrypsin inhibitor 2/inhibitory activity/loop flexibility/protein–protein interactions/stability/subtilisin BPN'

1 Present address: Department of Biochemistry, Chemistry Centre, University of Lund, PO Box 124, S- 22100 Lund, Sweden

2 To whom correspondence should be addressed


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