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: pavel.anzenbacher@upol.cz
Abstract
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