Engineering heme proteins

Huang LS, Wojciechowski G, Ortiz de Montellano PR (2006) Role of heme-protein covalent bonds in mammalian peroxidases - Protection of the heme by a single engineered heme-protein link in horseradish peroxidase. J Biol Chem 281 18983-18988... 

Gene shuffling and recombination has been used as a tool to engineer heme proteins. This research endeavor is aided by identification of exons and their corresponding protein structural units called modules. For example, human... 

Cytochrome c peroxidase (CCP) catalyzes the oxidation of ferrocytochrome c (cyt c). Many site-directed mutagenesis studies have been performed on this enzyme in efforts to better understand and rationally engineer heme peroxidase function [149 -156], Various studies indicate that the large protein substrate cyt c binds to CCP in a different region than smaller substrates [155, 157]. Whereas small substrates such as phenol and aniline are believed to approach the heme from its distal side and bind at the heme edge, cyt c lies much further from the heme, and electron transfer seems to occur from the proximal side [158], The low activity and selectivity exhibited by CCP compared to HRP and CPO is attributed to the limited access by small substrates to the heme [159]. 

Adjunct Professor of Physics at Utah State University. After completing her M. A. in Physics and PhD. in Biophysics at Harvard University, she became a member of the technical staff at AT T Bell Laboratories. She joined the USU faculty in 1988. She has a broad scope of expertise from biochemistry to electrical engineering, and has considerable experience in heme protein catalysis, structural biology, and the design and construction of optical and X-ray instrumentation. She was a pioneer the use of X-ray absorption spectroscopy for the investigation of biological problems and has authored more than 100 technical publications in refereed journals and books. 

Excellent examples of protein engineering work on dioxygenases are given in Section 10.8, changing the regio- and stereoselectivity on Rieske non-heme iron... 

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