Advertisement

Are all regions of folded proteins that undergo ligand-dependent order–disorder transitions targets for allosteric peptide mimetics?

Authors

  • Aron W. Fenton

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS
    • Correspondence to: Aron W. Fenton, Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, MS 3030, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA; e-mail: afenton@kumc.edu

    Search for more papers by this author

  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

ABSTRACT

Although the classical view of how proteins function relied on well folded structures, it is now recognized that the functions of many proteins are dependent on being intrinsically disordered. The primary consideration in this work is the intermediate group of proteins that are overall well folded, but which contain small regions that undergo order–disorder transitions. In particular, the current focus is on those order–disorder transitions that are energetically coupled to ligand binding. As exemplified by the case of human liver pyruvate kinase (hL-PYK), peptides that mimic the sequence of the order–disorder region can be used as allosteric regulators of the enzyme. On the basis of this example and others reported in the literature, we propose that a similar use of peptides that mimic protein regions that experience ligand-dependent order–disorder transitions can be a generalized initiation point for the development of allosteric drugs. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 553–557, 2013.

Ancillary