Differences in flexibility of active sites of cytochromes P450 probed by resonance Raman and UV-Vis absorption spectroscopy

J Inorg Biochem. 2001 Dec 15;87(4):209-13. doi: 10.1016/s0162-0134(01)00389-0.


Spectroscopic methods reveal differences in flexibility and stability of P450 forms. Among microsomal P450s, the most flexible active site has been found in the CYP3A4 enzyme as it is compressible and the heme vinyl side chains may adopt two different conformations. On the other hand, active site of this enzyme denatures quite easily upon hydrostatic pressure. The most rigid active site able to withstand the effect of high pressure has CYP1A2. The bacterial CYP102 (BM3) flavocytochrome has also a rather stable, but flexible active site. The differences between CYP3A4 and CYP1A2 active sites apparently reflect their ability to bind various substrates: whereas the CYP3A4 binds a vast variety of structures, the CYP1A2 preferentially binds planar, aromatic structures and its substrate specificity is relatively narrow.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoproteins / chemistry
  • Binding Sites
  • Cytochrome P-450 Enzyme System / chemistry*
  • Heme / chemistry
  • Humans
  • Protein Conformation
  • Protein Denaturation
  • Spectrophotometry
  • Spectrophotometry, Ultraviolet
  • Spectrum Analysis, Raman


  • Apoproteins
  • Heme
  • Cytochrome P-450 Enzyme System