Aug 22, 2006

The ins and outs of cytochrome P450s

Biochimica Et Biophysica Acta
Vlad CojocaruRebecca C Wade

Abstract

The active site of cytochromes P450 is situated deep inside the protein next to the heme cofactor. Consequently, enzyme specificity and kinetics can be influenced by how substrates pass through the protein to access the active site and how products egress from the active site. We previously analysed the channels between the active site and the protein surface in P450 crystal structures available in October 2003 [R.C. Wade, P.J. Winn, I. Schlichting, Sudarko, A survey of active site access channels in cytochromes P450, J. Inorg. Biochem. 98 (2004) 1175-1182]. Since then, 52 new P450 structures have been made available, including entries for ten isozymes for which structures were not previously available. We present an updated survey covering all P450 crystal structures available in March 2006. This survey shows channels not observed earlier in crystal structures, some of which were identified in previous molecular dynamics simulations. The crystal structures demonstrate how some of the channels can merge when the protein structure opens up resulting in a wide cleft to the active site, caused largely by movements of the F-G helix-loop-helix and the B-C loop. Significant differences were observed between the channels in the crysta...Continue Reading

  • References22
  • Citations126
  • References22
  • Citations126

Citations

Mentioned in this Paper

Molecular Dynamics
Molecular Helix
Enzymes, antithrombotic
Cytochrome P450
Helix (Snails)
Cytochrome P-450 Oxygenase
Cytochromes
Protein Conformation
Enzymes for Treatment of Wounds and Ulcers
CYP2B6 protein, human

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