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Updated: Sep 30, 2026

Modeling an Enzyme Active Site using Molecular Visualization Freeware
Published on: December 25, 2021
Plasticity of enzyme active sites
Annabel E Todd1, Christine A Orengo, Janet M Thornton
1Biochemistry and Molecular Biology Department, University College London, Gower Street, London, UK WC1E 6BT.
Abstract:
The expectation is that any similarity in reaction chemistry shared by enzyme homologues is mediated by common functional groups conserved through evolution. However, detailed enzyme studies have revealed the flexibility of many active sites, in that different functional groups, unconserved with respect to position in the primary sequence, mediate the same mechanistic role. Nevertheless, the catalytic atoms might be spatially equivalent. More rarely, the active sites have completely different locations in the protein scaffold. This variability could result from: (1) the hopping of functional groups from one position to another to optimize catalysis; (2) the independent specialization of a low-activity primordial enzyme in different phylogenetic lineages; (3) functional convergence after evolutionary divergence; or (4) circular permutation events.
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