Secondary Structure was predicted using the PredictProtein online application. The results show a helical structure (47.81%) with many connecting loops (45.42%) as well. The results indicate fewer beta strands in the structure than anything else ( <7%). The solvent accessibility predictor showed that the CYP molecule had mostly buried sequences (62.75%) with less exposed sequences (24.10%) , and even fewer intermediate sequences (13.15%).
Based on a comparison of the topology of many different enzymes, it is believed that all P450s have the same tertiary structure. The enzymes have similar tertiary structures, with a conserved core of secondary-structure elements. Most Cytochrome p450 are two-domain proteins that include the transmembrane and transmembrane helix domain.
In an analysis of the proteins based on the structure of P450 artificially created, it was proposed that the CYP3 family of proteins would adopt a similar tertiary structure (Hasemann et al. 1995). The general structure and functions of CYP's has been found through the study of a soluble cytochrome P450, P450cam. It was also proposed that there would be six locations in the primary sequence that would be potential substrate-recognition binding sites. However, the most significant difference found between CYP3A4 and other proteins is seen in helix D to H and the helix B to C regions (Yano et al. 2004). CYP3A4 proteins exhibit longer sequences between helices F and G that generally exhibit two additional helices, F′ and G′. This region is thought to form a membrane interaction domain, because the outer surfaces of these two helices are hydrophobic.
The shapes of the cavities differ in ways that are likely to affect substrate selectivity and enzyme catalysis, and this is the major difference between the secondary and tertiary structure of the proteins. The structure of 3A4 is much more open in the the active site. This larger active site is reflected in the changes that one of the six substrate-binding recognition sites is able to make when in the vicinity of heme iron.
In the CYP3A4 protein, helices F and G do not pass over the active site cavity in 3A4 because these helices are shorter, making the active site more attainable. The atypical structure of the helices in CYP3A4 over the active site accommodate the simultaneous binding of multiple molecules, making CYP3A4 one of the most biologically relevant CYP proteins.
- Alessandra: Cytochrome p450: Introduction
- Alessandra: Cytochrome p450: Biological function
- Alessandra: Cytochrome p450: Biosynthesis
- Alessandra: Cytochrome p450: Gene sequence
- Alessandra: Cytochrome p450: Amino acid sequence and composition
- Alessandra: Cytochrome p450: Secondary and tertiary structure
- Alessandra: Cytochrome p450: Domains and structural motifs
- Alessandra: Cytochrome p450: Interactions with macromolecules and small molecules
- Alessandra: Cytochrome p450: Molecular biodiversity and evolution
- Alessandra: Cytochrome p450: Literature overview
- Alessandra: Cytochrome p450: Useful online resources
Hasemann, Charles A., Ravi G. Kurumbali, Sekhar S. Boddupalli, Julian A. Peterson, and Johann Deisenhofer. "Structure and Function of Cytochromes P450: A Comparative Analysis of Three Crystal Structures ." Structure 3.1 (1995): 41-62.Science Direct. Web. 3 Mar. 2014.
Yano, Jason K., Michael R. Wester, Guillaume A. Schoch, Keith J. Griffin, C. David Stout, and Eric F. Johnson. "The Structure of Human Microsomal Cytochrome P450 3A4 Determined by X-ray Crystallography to 2.05-Å Resolution. " The Journal of Biological Chemistry 279 (2004): 91-94. JBC.org. Web. 10 Mar. 2014.
Secondary Structrure found using PredictProtein