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Structure-Guided Recombination Creates an Artificial Family of Cytochromes P450
 

Summary: Structure-Guided Recombination Creates
an Artificial Family of Cytochromes P450
Christopher R. Otey1
, Marco Landwehr2
, Jeffrey B. Endelman3
, Kaori Hiraga2
, Jesse D. Bloom2
, Frances H. Arnold1,2,3*
1 Biochemistry and Molecular Biophysics, California Institute of Technology, Pasadena, California, United States of America, 2 Division of Chemistry and Chemical
Engineering, California Institute of Technology, Pasadena, California, United States of America, 3 Bioengineering, California Institute of Technology, Pasadena, California,
United States of America
Creating artificial protein families affords new opportunities to explore the determinants of structure and biological
function free from many of the constraints of natural selection. We have created an artificial family comprising ;3,000
P450 heme proteins that correctly fold and incorporate a heme cofactor by recombining three cytochromes P450 at
seven crossover locations chosen to minimize structural disruption. Members of this protein family differ from any
known sequence at an average of 72 and by as many as 109 amino acids. Most (.73%) of the properly folded chimeric
P450 heme proteins are catalytically active peroxygenases; some are more thermostable than the parent proteins. A
multiple sequence alignment of 955 chimeras, including both folded and not, is a valuable resource for sequence-
structure-function studies. Logistic regression analysis of the multiple sequence alignment identifies key structural
contributions to cytochrome P450 heme incorporation and peroxygenase activity and suggests possible structural

  

Source: Arnold, Frances H. - Division of Chemistry and Chemical Engineering, California Institute of Technology

 

Collections: Chemistry; Biology and Medicine