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Int. J. Mol. Sci. 2015, 16(9), 22735-22753; doi:10.3390/ijms160922735

Effects of Non-Natural Amino Acid Incorporation into the Enzyme Core Region on Enzyme Structure and Function

Department of Chemical Engineering, University of Virginia, Charlottesville, VA 22904, USA
School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea
Author to whom correspondence should be addressed.
Academic Editor: Qiang “Shawn” Chen
Received: 12 August 2015 / Revised: 2 September 2015 / Accepted: 14 September 2015 / Published: 21 September 2015
(This article belongs to the Special Issue Protein Engineering)
View Full-Text   |   Download PDF [1323 KB, uploaded 21 September 2015]   |  


Techniques to incorporate non-natural amino acids (NNAAs) have enabled biosynthesis of proteins containing new building blocks with unique structures, chemistry, and reactivity that are not found in natural amino acids. It is crucial to understand how incorporation of NNAAs affects protein function because NNAA incorporation may perturb critical function of a target protein. This study investigates how the site-specific incorporation of NNAAs affects catalytic properties of an enzyme. A NNAA with a hydrophobic and bulky sidechain, 3-(2-naphthyl)-alanine (2Nal), was site-specifically incorporated at six different positions in the hydrophobic core of a model enzyme, murine dihydrofolate reductase (mDHFR). The mDHFR variants with a greater change in van der Waals volume upon 2Nal incorporation exhibited a greater reduction in the catalytic efficiency. Similarly, the steric incompatibility calculated using RosettaDesign, a protein stability calculation program, correlated with the changes in the catalytic efficiency. View Full-Text
Keywords: non-natural amino acids; enzyme engineering; enzyme kinetics; site-specific incorporation non-natural amino acids; enzyme engineering; enzyme kinetics; site-specific incorporation

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wong, H.E.; Kwon, I. Effects of Non-Natural Amino Acid Incorporation into the Enzyme Core Region on Enzyme Structure and Function. Int. J. Mol. Sci. 2015, 16, 22735-22753.

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