CHAPTER 18: Recent Advances in the Structural and Mechanistic Biology of Non-Haem Fe(ii), 2-Oxoglutarate and O2-Dependent Halogenases
Published:23 Apr 2015
Janet L. Smith, Dheeraj Khare, 2015. "Recent Advances in the Structural and Mechanistic Biology of Non-Haem Fe(ii), 2-Oxoglutarate and O2-Dependent Halogenases", 2-Oxoglutarate-Dependent Oxygenases, Christopher Schofield, Robert Hausinger
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A growing number of halogenases have been characterized that use non-haem iron, 2-oxoglutarate and molecular oxygen to enable catalysis via a substrate-free radical at the site of halogenation. The halogenases and related hydroxylases have near identical reaction mechanisms, leading to outstanding questions about what determines whether transfer of halide or hydroxyl resolves the substrate-free radical. Intriguing results indicate that the position of the substrate in the active site is a strong determinant of reaction outcome. All the halogenases are found in natural product biosynthetic pathways, and their substrates are covalently tethered to the phosphopantetheine cofactor of a carrier protein. Crystal structures for three halogenases show a remarkable degree of tailoring of the active site for the biological function of each enzyme.