Reconciling the lock-and-key and dynamic views of canonical serine protease inhibitor action

Varnai, Peter, Gáspári, Zoltan, Szappanos, Balazs and Perczel, Andras (2010) Reconciling the lock-and-key and dynamic views of canonical serine protease inhibitor action. FEBS Letters, 584 (1). pp. 203-206. ISSN 0014-5793

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Abstract

The efficiency of canonical serine protease inhibitors is conventionally attributed to the rigidity of their protease binding loop with no conformational change upon enzyme binding, yielding an example of the lock-and-key model for biomolecular interactions. However, solution-state structural studies revealed considerable flexibility in their protease binding loop. We resolve this apparent contradiction by showing that enzyme binding of small, 35-residue inhibitors is actually a dynamic conformer selection process on the nanosecond-timescale. Thus, fast timescale dynamics enables the association rate to be solely diffusion-controlled just like in the rigid-body model.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Depositing User: Peter Varnai
Date Deposited: 06 Feb 2012 19:18
Last Modified: 15 Jun 2012 11:15
URI: http://sro.sussex.ac.uk/id/eprint/20010
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