Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels.

ABSTRACT: Cells contain numerous enzymes that use molecular oxygen for their reactions. Often, their active sites are buried deeply inside the protein, which raises the question whether there are specific access channels guiding oxygen to the site of catalysis. Choosing 12/15-lipoxygenase as a typical example for such oxygen-dependent enzymes, we determined the oxygen distribution within the protein and defined potential routes for oxygen access. For this purpose, we have applied an integrated strategy of structural modeling, molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements. First, we computed the 3D free-energy distribution for oxygen, which led to identification of four oxygen channels in the protein. All channels connect the protein surface with a region of high

SUBMITTER: Saam J 

PROVIDER: S-EPMC1948941 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature