Introduction

Cytochromes P450 form a superfamily heme-thiolate biocatalysts (oxidoredictases). In all living organisms, we can always  find a few forms (with the exception of Enterobacteriaceae such as Escherichia coli). However, their number can vary dramatically. While the bacteria has more than 20 forms of CYPs in humans there are currently 57 known and in plants this number varies about 300. [1, 2]

Cytochrome P450 system are the most important first phase metabolism of endogenous substances (eg. steroids, fatty acids), but if exogenous or xenobiotics (eg. drugs, food additives, aerosols). Participate in the biotransformation of approximately 50% of all administered drugs whose metabolism is unknown. The task of phase I. is the conversion of substrate to the electrophilic intermediate. It is in the second metabolized to hydrophilic phase derivative and subsequently expelled bodily fluids. The chemical processes taking place in the active site, which is buried inside the structure and is accessible only via the access roads or canals / tunnels. Cytochromes are located primarily in the liver, brain, lung, kidneys, placenta and intestine. [3, 4]

The discovery dates back to 1958, which contributed to the characterization of T. Omura and R. Sato. [5] The human cytochrome P450 attract the attention of scientists precisely because it is significantly involved in the metabolism of xenobiotics. At the end of 2006 was crystallized seven mammalian forms of these enzymes (5 of them human) and published in seventeen structures (11 of them human). [6]
Detailed analysis of cytochrome P450 can help determine whether the drugs act as a substrate, inducer or inhibitor. This knowledge will support the regulation of drug administration and the anticipation of adverse events (clinically significant drug interactions that may lead to drug toxicity, reduce or increase the contrast of pharmacological effects).

The completion of these projects, it is necessary to assess the structural properties of the access routes to the active site and then find the common features and differences between different forms of cytochrome particularly in terms of their length, preferences, presence and orientation of residues. This appreciation is to my work, which together with the study of enzyme flexibility should help to understanding the mechanism of function of cytochrome P450 primarily in xenobiotic metabolism. Flexibility as the second essential factor is not the subject of this research.