Homology modeling of plant cytochrome P450s

Plant P450 monooxygenases represent the largest family of plant proteins and the largest collection of P450s available for comparative studies and biotechnological applications. They have been shown to catalyze a diverse array of difficult chemical reactions and have demonstrated potential to be used in pharmacological, agronomic and phytoremediative applications. Central to our use of these catalytically competent enzymes is the need to understand their interactions with substrates. Because most characterized plant P450s are membrane-bound proteins that are resistant to standard X-ray and NMR structure determinations, homology modeling represents a reliable and relatively rapid alternative method for analyzing structure-function relationships and predicting substrates for many P450s that are only now being characterized. These methods, which are being widely used in mammalian P450 structure-function studies, can allow plant biologists to define critical residues interacting with substrates and, in a directed fashion, alter the reactivities of individual monooxygenases. The homology modelings that have been done on a limited number of plant P450s and the site-directed mutations that validate them indicate that current modeling and substrate docking procedures are capable of providing structural explanations for sequence variants as well as for predicting functional characteristics of undefined P450s.