De novo design of catalytic proteins.
The de novo design of catalytic proteins provides a stringent test of our understanding of enzyme function, while simultaneously laying the groundwork for the design of novel catalysts. Here we describe the design of an O(2)-dependent phenol oxidase whose structure, sequence, and activity are designed from first principles. The protein catalyzes the two-electron oxidation of 4-aminophenol (k(cat)/K(M) = 1,500 M(-1).min(-1)) to the corresponding quinone monoimine by using a diiron cofactor. The catalytic efficiency is sensitive to changes of the size of a methyl group in the protein, illustrating the specificity of the design.
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6059, USA.
J
J
Kaplan
W F
WF
DeGrado
D000627:Aminophenols; D002384:Catalysis; D015195:Drug Design; D004798:Enzymes / Q000138:chemical synthesis / Q000737:chemistry; D007501:Iron; D007700:Kinetics; D018716:Molecular Mimicry; D014442:Monophenol Monooxygenase / Q000138:chemical synthesis* / Q000737:chemistry; D010100:Oxygen / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D011809:Quinones / Q000138:chemical synthesis; D013329:Structure-Activity Relationship
D000627:Aminophenols; D004798:Enzymes; D011809:Quinones; D007501:Iron; D014442:Monophenol Monooxygenase; C026729:4-aminophenol; D010100:Oxygen