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Science 19 August 1988:
Vol. 241. no. 4868, pp. 976 - 978
DOI: 10.1126/science.3043666
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Articles

Science, Vol 241, Issue 4868, 976-978
Copyright © 1988 by American Association for the Advancement of Science

articles

Characterization of a helical protein designed from first principles

L Regan and WF DeGrado

E. I. du Pont de Nemours & Company, Central Research & Development Department, Wilmington, DE 19898.

The question of how the primary amino acid sequence of a protein determines its three-dimensional structure is still unanswered. One approach to this problem involves the de novo design of model peptides and proteins that should adopt desired three-dimensional structures. A systematic approach was aimed at the design of a four-helix bundle protein. The gene encoding the designed protein was synthesized and the protein was expressed in Escherichia coli and purified to homogeneity. The protein was shown to be monomeric, highly helical, and very stable to denaturation by guanidine hydrochloride (GuHCl). Thus a globular protein has been designed that is capable of adopting a stable, folded structure in aqueous solution.


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Crystal structure of alpha 1: implications for protein design.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)