Cytochrome P450 1A1 opens up to new substrates

J Biol Chem. 2018 Dec 14;293(50):19211-19212. doi: 10.1074/jbc.H118.006715. Epub 2018 Dec 14.

Abstract

The cytochromes P450 (CYPs) oxidatively transform a huge number of substrates in both prokaryotic and eukaryotic organisms, but the mechanisms by which they accommodate these diverse molecules remain unclear. A new study by Bart and Scott reports two co-crystal structures of CYP1A1 that reveal structural rearrangements and flexible interaction networks that explain how the active site cavity shapes itself around new ligands. These data open the door to an increased understanding of fundamental enzyme behavior and improved searches for anti-cancer compounds.

Publication types

  • Introductory Journal Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Cytochrome P-450 CYP1A1 / chemistry
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism*
  • Erlotinib Hydrochloride / chemistry
  • Erlotinib Hydrochloride / metabolism*
  • Furocoumarins / chemistry
  • Furocoumarins / metabolism*
  • Humans
  • Ligands
  • Protein Binding
  • Substrate Specificity

Substances

  • Enzyme Inhibitors
  • Furocoumarins
  • Ligands
  • Erlotinib Hydrochloride
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1
  • bergamottin