The X-ray structure of epoxide hydrolase from Agrobacterium radiobacter AD1 - An enzyme to detoxify harmful epoxides

Epoxide hydrolases catalyze the cofactor-independent hydrolysis of reactive and toxic epoxides, They play an essential role in the detoxification of v arious xenobiotics in higher organisms and in the bacterial degradation of several environmental pollutants. The first x-ray structure of one of these , from Agrobacterium radiobacter AD1, has been determined by isomorphous re placement at 2.1-Angstrom resolution. The enzyme shows a two domain structu re with the core having the alpha/beta hydrolase-fold topology. The catalyt ic residues, Asp(107) and His(275), are located in a predominantly hydropho bic environment between the two domains. A tunnel connects the back of the active-site cavity with the surface of the enzyme and provides access to th e active site for the catalytic water molecule, which in the crystal struct ure, has been found at hydrogen bond distance to His275. Because of a cryst allographic contact, the active site has become accessible for the Gln(134) side chain, which occupies a position mimicking a bound substrate. The str ucture suggests Tyr(152)/Tyr(215) as the residues involved in substrate bin ding, stabilization of the transition state, and possibly protonation of th e epoxide oxygen.