O2 reactivity of flavoproteins: dynamic access of dioxygen to the active site and role of a H+ relay system in D-amino acid oxidase.

ABSTRACT: Molecular dynamics simulations and implicit ligand sampling methods have identified trajectories and sites of high affinity for O(2) in the protein framework of the flavoprotein D-amino-acid oxidase (DAAO). A specific dynamic channel for the diffusion of O(2) leads from solvent to the flavin Si-side (amino acid substrate and product bind on the Re-side). Based on this, amino acids that flank the putative O(2) high affinity sites have been exchanged with bulky residues to introduce steric constraints. In G52V DAAO, the valine side chain occupies the site that in wild-type DAAO has the highest O(2) affinity. In this variant, the reactivity of the reduced enzyme with O(2) is decreased >or=100-fold and the turnover number approximately 1000-fold thus verifying the concept. In addition, the sim

SUBMITTER: Saam J 

PROVIDER: S-EPMC2915680 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature