Second-Coordination Sphere Effects on Selectivity and Specificity of Heme and Nonheme Iron Enzymes |
| |
Authors: | Dr Sam P de Visser |
| |
Institution: | The Manchester Institute of Biotechnology and Department of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester, M1 7DN UK |
| |
Abstract: | Mononuclear iron-containing enzymes are highly versatile oxidants that often react stereospecifically and/or regioselectively with substrates. Combined experimental and computational studies on heme monooxygenases, nonheme iron dioxygenases and halogenases have revealed the intricate details of the second-coordination sphere, which determine this specificity and selectivity. These second-coordination sphere effects originate from the positioning of the substrate and oxidant, which involve the binding of the co-factors and substrate into the active site of the protein. In addition, some enzymes affect the selectivity and reactivity through charge-stabilization from nearby bound cations/anions, an induced electric field or through the positioning of salt bridges and hydrogen-bonding interactions to first-coordination sphere iron ligands and/or the substrate. Examples of all of these second-coordination sphere effects in iron-containing enzymes and how these influence structure and reactivity are given. |
| |
Keywords: | computational modeling cytochrome P450 enzyme mechanisms hydroxylation nonheme iron dioxygenases |
|
|