Paper Citing NAMD - Abstract
De Luna, Phil; Bushnell, Eric A. C.; Gauld, James W.
A Molecular Dynamics Examination on Mutation-Induced Catalase Activity in Coral Allene Oxide Synthase
JOURNAL OF PHYSICAL CHEMISTRY B, 117:14635-14641, NOV 28 2013
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-hydro-peroxyeicosatetraenoic) 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 (FeO2H2)-O-... interaction. In addition, the His67(...)H(2)O(2) distance shortens considerably, increasing the likelihood of a Cpd I intermediate and hence exhibiting catalase activity.
