Allosteric control of proteins by manipulating mechanical...

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease

Reexamination Certificate

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C435S015000, C435S006120, C530S350000, C536S023100

Reexamination Certificate

active

08008053

ABSTRACT:
A method of altering the conformation of a polypeptide having a known three-dimensional structure is described. The method comprises attaching a first end of a polymer to a first portion of the polypeptide, attaching a second end of the polymer to a second portion of the polypeptide, and altering the mechanical tension of the polymer, thereby altering the conformation of the polypeptide. The alteration of the conformation of the polypeptide may increase or decrease the binding affinity of the polypeptide for a substrate bound by the polypeptide, or alter the catalytic rate of an enzyme. Typically, the polymer is a polynucleotide or polypeptide.

REFERENCES:
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Branden et al., Introduction to Protein Structure, Garland Publishing Inc., New York, p. 247, 1991.
Witkowski et al., Biochemistry 38:11643-11650, 1999.
Seffernick et al., J. Bacteriol. 183(8):2405-2410, 2001.
Choi, Brian, et al., “Artificial Allosteric Control of Maltose Binding Protein” Annual Mtg. of the Amer. Phys. Soc., Mar. 22-26, 2004, Canada, Abstract.
Zocchi, Giovani, “Artificial Allosteric Control of Maltose-Binding Protein” APACS, v. 228, Part 2, Aug. 2004 pp. U290.
Kramer, Richard, “Spanning Binding Sites on Allosteric Proteins with Polymer-Linked Ligand Dimers”, Nature, (London) V395, N6703, Oct. 15, 1998, pp. 710-713.
Choi, Brian, “Artificial Allosteric Control of Maltose Binding Protein”, Phys. Review Letters, Jan. 28, 2005, V94, No. 3, pp. 38103.
Choi, Brian, “Allosteric Control Through Mechanical Tension”, Pnys, Review Letters, Aug. 12, 2005, V95 No. 7, pp. 78102.

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