PMID: 9169606May 1, 1997Paper

Synthetic, structural and biological studies of the ubiquitin system: synthesis and crystal structure of an analogue containing unnatural amino acids

The Biochemical Journal
S G LoveR J Mayer

Abstract

Ubiquitin is a 76-amino acid protein involved in the targeting for destruction of proteins in the cell. The protein can readily be synthesized chemically affording an extra dimension to studies of protein stability. Ubiquitin with various modifications to the hydrophobic core has been synthesized. In particular, two core amino acids have been replaced by aminobutyric acid (Val-26) and norvaline (for Ile-30) and the product crystallized. The refined crystal structure shows an overall contraction of the molecule and the side chain of Nva-30 rotates relative to Ile-30. However, the side chain rotation is not sufficient to compensate for the effect of the loss of the methyl group and hence a small cavity is introduced into the structure, which decreases the stability of the protein. The biological behaviour of the modified protein is unaltered. The observed changes in stability are of the magnitude expected for the removal of methyl groups from the hydrophobic core of a protein. Interestingly, the effect appears to be independent of the position of the removed methyl group. The intact structure, but not its stability, is important for recognition by the biological conjugating system.

Citations

Dec 1, 2010·Angewandte Chemie·Farid El OualidHuib Ovaa
May 7, 2019·Chembiochem : a European Journal of Chemical Biology·Halina M WernerW Seth Horne
Jun 15, 2012·Angewandte Chemie·Liat Spasser, Ashraf Brik
Aug 15, 2014·The Journal of Biological Chemistry·Lei GuZhefeng Guo
Apr 12, 2013·Biopolymers·Caroline E WellerChampak Chatterjee
Dec 19, 2012·Journal of the American Society for Mass Spectrometry·Jong Wha LeeHugh I Kim
May 19, 2016·The Journal of Physical Chemistry. B·Qichi Hu, Julia Laskin

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