title: A molecular dynamics examination on mutation-induced catalase activity in coral allene oxide synthase.
abstract: Coral allene oxide synthase (cAOS) catalyzes the formation of allene oxides from fatty acid hydroperoxides. Interestingly, its active site differs from that of catalase by only a single residue yet is incapable of catalase activity. That is, it is unable to catalyze the decomposition of hydrogen peroxide to molecular oxygen and water. However, the single active-site mutation T66V allows cAOS to exhibit catalase activity. We have performed a series of molecular dynamics (MD) simulations in order to gain insights into the differences in substrate (8R-hydroperoxyeicosatetraenoic) and H2O2 active site binding between wild-type cAOS and the T66V mutant cAOS. It is observed that in wild-type cAOS the active site Thr66 residue consistently forms a strong hydrogen-bonding interaction with H2O2 (catalase substrate) and, importantly, with the aid of His67 helps to pull H2O2 away from the heme Fe center. In contrast, in the T66V-cAOS mutant the H2O2 is much closer to the heme's Fe center and now forms a consistent Fe···O2H2 interaction. In addition, the His67···H2O2 distance shortens considerably, increasing the likelihood of a Cpd I intermediate and hence exhibiting catalase activity.
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor , Windsor, Ontario N9B 3P4, Canada.
authors.forename: Phil
authors.initials: P
authors.lastname: De Luna
authors.forename: Eric A C
authors.initials: EA
authors.lastname: Bushnell
authors.forename: James W
authors.initials: JW
authors.lastname: Gauld
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D002374:Catalase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020134:Catalytic Domain; D006861:Hydrogen Peroxide / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation
chemical_list: D006861:Hydrogen Peroxide; D002374:Catalase; D019746:Intramolecular Oxidoreductases; C021377:hydroperoxide isomerase