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Trends Biochem Sci. 2005 Nov;30(11):622-9. Epub 2005 Oct 7.

Understanding nature's catalytic toolkit.

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EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.


Enzymes catalyse numerous reactions in nature, often causing spectacular accelerations in the catalysis rate. One aspect of understanding how enzymes achieve these feats is to explore how they use the limited set of residue side chains that form their 'catalytic toolkit'. Combinations of different residues form 'catalytic units' that are found repeatedly in different unrelated enzymes. Most catalytic units facilitate rapid catalysis in the enzyme active site either by providing charged groups to polarize substrates and to stabilize transition states, or by modifying the pKa values of other residues to provide more effective acids and bases. Given recent efforts to design novel enzymes, the rise of structural genomics and subsequent efforts to predict the function of enzymes from their structure, these units provide a simple framework to describe how nature uses the tools at her disposal, and might help to improve techniques for designing and predicting enzyme function.

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