CYP crystal structures

Comparative Analysis Between the Different CYP Crystal Structures... 

Recently, several CYP crystal structures have been deposited in the P D B and could be used to understand the different metabolic properties. From the analysis of the different protein structures, it could be concluded that in general CYPs maintain the secondary elements across the different subfamilies, but they have a quite high flexibility, accommodating the protein structures to the ligand bound in the enzyme cavity. 

Table 1 Selection of 52 of the 120 CYP Homology Models Built So Far Based on Available CYP Crystal Structures... 

The analysis of the cytochrome crystal structures reveals extensive differences among the mammalian and the human CYPs that may reflect the structural flexibility of these enzymes and therefore the broad substrate specificity observed. In general, the secondary elements and the overall structure of the CYP are conserved. Nevertheless, it seems that in most enzymes, the most flexible regions are located between the F-G helixes and the B-C loop. For example in the CYP2B4 apoprotein (lpo5) the... 

The Pathfinder approach was used to compare the CYP cavities of CYP2C9 [8], 2D6 [9], and 3A4 [10], the most important human cytochrome enzymes. CYP2C9 and 3A4 were available as protein crystal structures whilst an homology model was used for 2D6. Frequency distribution plots (Fig. 5.8) were obtained from non-superposed CYP structures, selecting the iron in the heme moiety as a root departure path. 

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