Active Sites of Cytochromes P450: What are They Like?
Pavel Anzenbacher1*, Eva Anzenbacherová2, Reinhard Lange3, Josef Skopalík4 and Michal Otyepka4
1 Department of Pharmacology Faculty of Medicine and Dentistry, Palacky
University at Olomouc, Hnevotinska 3,
CZ-775 15 Olomouc, Czech Republic
2 Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University at Olomouc, Hnevotinska 3, CZ-775 15 Olomouc, Czech Republic
3 INSERM U710, University of Montpellier 2, 34095 Montpellier Cedex 5, France
4 Department of Physical Chemistry, Faculty of Sciences, Palacky University at Olomouc, Svobody 26, CZ-771 46 Olomouc, Czech Republic
* Corresponding author: E-mail: firstname.lastname@example.org
Although the x-ray crystallography is giving a relatively precise picture of spatial arrangement of the majority of protein structure, it is not able to give detailed information on the flexibility of the protein active site. The properties of active sites of cytochromes P450 (CYP) were supposed earlier to be relatively similar, reflecting the substrate specificities of the individual enzymes mainly by the amino acid residues present in the respective active site. On the other hand, the most recent experimental as well as theoretical results document that it is the flexibility of this part of protein which gives the active site the property to bind substrates correctly and to accommodate them. It is also the flexibility or plasticity of the structure which determines or limits the property of the protein to keep the conformation which guarantees the function of the enzyme.
Keywords: Cytochromes P450, active sites, protein flexibility, protein compressibility, molecular dynamics