Correction

Chloroperoxidase-Catalyzed Epoxidation ofcis-β-Methylstyrene: Distal Pocket Flexibility Tunes Catalytic Reactivity

“…This is in line with a Glu183His mutant experimental study indicating that a distortion of the His105-Glu183 proton shuttle favors epoxidation over other catalytic reactions . These results led to the intuitively attractive postulate , that the epoxidation activity of CPO requires distal pocket flexibility so that the native polar, peroxidase-like environment of the active center can be changed into the hydrophobic environment characteristic of P450. In previous work, we demonstrated that the enantiospecificity of the epoxidation reaction is not correlated with the relative favorability of particular prechiral binding complexes but is likely to be correlated with the effect of the distal pocket on the transition state .…”

“…The position and acid–base properties of the Glu183 carboxylate side chain are affected by hydrogen bonding with the imidazole side chain of His105 (Figure ). ,, Together, His105 and Glu183 have been referred to as a proton shuttle; the shuttle’s role in catalyzing CPO-I formation is well established. , The results of Glu183His mutation and His105 alkylation suggest that these two residues affect not only Cpd I formation but also CPO-catalyzed oxidations. In addition to His105 and Glu183, the distal pocket contains a set of hydrophobic residues surrounding the active center. , This hydrophobic core of residues constitutes most of the steric environment of the active center and is probably the primary cause of the stereoselectivity of oxidations carried out by CPO. ,, …”

“…Despite this wealth of knowledge concerning model Cpd I systems, the influence of the CPO environment, in particular the distal pocket, on the mechanism of the epoxidation reaction has hardly been explored. Elucidating the nature of this influence is expected to yield understanding of CPO’s catalytic versatility ,, and of the enantiospecificity of the epoxidation reaction. ,, The ability of CPO to catalyze many P450-type reactions implies that such a result could also further our understanding of the catalytic functions of P450s, which participate in key biochemical processes in many living species …”

“…The role of the distal pocket environment in CPO-catalyzed epoxidation of an olefinic substrate, cis -β-methylstyrene (CBMS), is the focus of this paper. CPO-catalyzed epoxidation of CBMS is of potential interest for pharmaceutical applications and has been the subject of a number of studies. ,,, CBMS is converted by CPO-I into 1S2R and 1R2S epoxides with a 96:4 ratio . Thus it is a system of choice for understanding the source of CPO’s epoxidation enantiospecificity.…”

“…These results led to the intuitively attractive postulate , that the epoxidation activity of CPO requires distal pocket flexibility so that the native polar, peroxidase-like environment of the active center can be changed into the hydrophobic environment characteristic of P450. In previous work, we demonstrated that the enantiospecificity of the epoxidation reaction is not correlated with the relative favorability of particular prechiral binding complexes but is likely to be correlated with the effect of the distal pocket on the transition state . To complete the assessment of the distal pocket’s effect on the reaction barrier, extensive conformational sampling of the transition state modeled with the entire enzyme flexible is required.…”