References & Sources

Making the Cut
Scientists exploit proteins that perform surgery upon themselves

Some proteins contain a portion that cuts itself out and melds the two remaining fragments together to form the final, active molecule.

References:

Camarero, J.A., and T.W. Muir. 1999. Biosynthesis of a head-to-tail cyclized protein with improved biological activity. Journal of the American Chemical Society 121(June 16):5597.

Cotton, G.J. . . . and T.W. Muir. 1999. Insertion of a synthetic peptide into a recombinant protein framework: A protein biosensor. Journal of the American Chemical Society 121(Feb. 10):1100.

Evans Jr., T.C., J. Benner, and M.-Q. Xu. 1999. The cyclization and polymerization of bacterially expressed proteins using modified self-splicing inteins. Journal of Biological Chemistry 274(June 25):18359.

______. 1998. Semisynthesis of cytotoxic proteins using a modified protein splicing element. Protein Science 7:2256.

Perler, F.B. 1998. Protein splicing of inteins and hedgehog autoproteolysis: Structure, function, and evolution. Cell 92(Jan. 9):1.

Wood, D.W. . . . and M. Belfort. 1999. A genetic system yields self-cleaving inteins for bioseparations. Nature Biotechnology 17(September):889.

Wu, H., Z. Hu, and X.-Q. Liu. 1998. Protein trans-splicing by a split intein encoded in a split DnaE gene of Synechocystis sp. PCC6803. Proceedings of the National Academy of Sciences 95(Aug. 4):9226.

Xu, R. . . . and T.W. Muir. 1999. Chemical ligation of folded recombinant proteins: Segmental isotopic labeling of domains for NMR studies. Proceedings of the National Academy of Sciences 96(Jan. 19):388.

Further Readings:

Amitai, G., and S. Pietrokovski. 1999. Fine-tuning an engineered intein. Nature Biotechnology 17(September):854.

Cotton, G.J., and T.W. Muir. 1999. Peptide ligation and its application to protein engineering. Chemistry & Biology 6(September):R247.

Yu, H. 1999. Extending the size limit of protein nuclear magnetic resonance. Proceedings of the National Academy of Sciences 96(Jan. 19):332.

Additional information about inteins can be found at http://blocks.fhcrc.org/~pietro/inteins/.

Sources:

Marlene Belfort
New York State Department of Health
Wadsworth Center
Albany, NY 12201-2002

Thomas C. Evans Jr.
New England Biolabs, Inc.
32 Tozer Road
Beverly, MA 01915-5599

Xiang-Qin Liu
Dalhousie University
Biochemistry Department
Halifax, Nova Scotia B3H 4H7
Canada

Tom W. Muir
Rockefeller University
Laboratory of Synthetic Protein Chemistry
1230 York Avenue
New York, NY 10021

Henry Paulus
Boston Biomedical Research Institute
20 Staniford Street
Boston, MA 02114

Francine B. Perler
New England Biolabs, Inc.
32 Tozer Road
Beverly, MA 01915-5599

Ming-Qun Xu
New England Biolabs, Inc.
32 Tozer Road
Beverly, MA 01915-5599

From Science News, Vol. 156, No. 14, October 2, 1999, p. 222. Copyright © 1999, Science Service.