3D-QSAR/CoMFA Models as aTool for Biocatalysis and Protein Engineering

J. D. Carballeira Rodríguez, E. Alvarez Ruiz and J. V. Sinisterra Gago

Abstract
The x-ray structure of an enzyme is taken into account, when available, as the reference model to explain catalytic activity and selectivity. Unfortunately, in most of the cases the structure is available only as apostructure, i.e. without the substrate bound to the active site, and it is strange to find many different enzyme-substrate complexes of a specific enzyme as crystals. Moreover this structure is not the "real" structure of the protein during catalysis as the crystal is stationary. In this paper we propose the use of CoMFA models to evaluate the differences between the crystal and the real structure of the enzyme under reaction conditions. In addition to the stationary nature of a crystal, the experimental limitations of crystallographic techniques to obtain crystals in a fast and reliable manner, give a chance to the creation of CoMFA models by evaluating the easy to obtain catalytic properties of enzyme variants to provide information about the structural changes produced by the mutations. By means of the evaluation of different structures as substrates CoMFA models will not only provide information about the structure of the enzyme, but also about the flexibility and potential conformational changes of the substrate binding site.

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Keywords
Biotransformations, activity models, enzyme structure