May 08 2004
Bernat B, Sun M, Dwyer M, Feldkamp M, Kossiakoff AA
Biochemistry 2004 May;43(20):6076-84
PMID: 15147191
Abstract
Phage display mutagenesis is a widely used approach to engineering novel protein properties and is especially powerful in probing structure-function relationships in molecular recognition processes. The relative contributions of additive and cooperative binding forces and the influence of conformational …
Sep 08 2003
Walsh ST, Jevitts LM, Sylvester JE, Kossiakoff AA
Protein Sci. 2003 Sep;12(9):1960-70
PMID: 12930995
Abstract
Receptor signaling in the growth hormone (GH)-growth hormone receptor (GHR) system is controlled through a sequential two-step hormone-induced dimerization of two copies of the extracellular domain (ECD) of the receptor. The regulatory step of this process is the binding of …
Sep 08 2003
Pal G, Kossiakoff AA, Sidhu SS
J. Mol. Biol. 2003 Sep;332(1):195-204
PMID: 12946357
Abstract
A high-affinity variant of human growth hormone (hGH(v)) contains 15 mutations within site 1 and binds to the hGH receptor (hGHR) approximately 400-fold tighter than does wild-type (wt) hGH (hGH(wt)). We used shotgun scanning combinatorial mutagenesis to dissect the energetic contributions …
Jun 08 2003
Pál G, Santamaria F, Kossiakoff AA, Lu W
Protein Expr. Purif. 2003 Jun;29(2):185-92
PMID: 12767808
Abstract
Selective incorporation of non-natural amino acid residues into proteins is a powerful approach to delineate structure-function relationships. Although many methodologies are available for chemistry-based protein engineering, more facile methods are needed to make this approach suitable for routine laboratory …
Feb 08 2003
Bernat B, Pal G, Sun M, Kossiakoff AA
Proc. Natl. Acad. Sci. U.S.A. 2003 Feb;100(3):952-7
PMID: 12552121
Abstract
Signaling in the human growth hormone (hGH)-human GH receptor system is initiated by a controlled sequential two-step hormone-induced dimerization of two hGH receptors via their extracellular domains (ECDs). Little is currently known about the energetics governing the …
Feb 08 2002
Schiffer C, Ultsch M, Walsh S, Somers W, de Vos AM, Kossiakoff A
J. Mol. Biol. 2002 Feb;316(2):277-89
PMID: 11851338
Abstract
The structure of the ternary complex between the phage display- optimized, high-affinity Site 1 variant of human growth hormone (hGH) and two copies of the extracellular domain (ECD) of the hGH receptor (hGHR) has …
Nov 08 2001
Dwyer JJ, Dwyer MA, Kossiakoff AA
Biochemistry 2001 Nov;40(45):13491-500
PMID: 11695896
Abstract
Using phage display mutagenesis, high affinity variants of RNase S-peptide were produced that bind to RNase S-protein over 100-fold more tightly than the wild type S-peptide. The S-peptide: S-protein interface was further characterized using “biased” phage display libraries, where each targeted residue was …
Apr 08 2000
Dwyer MA, Lu W, Dwyer JJ, Kossiakoff AA
Chem. Biol. 2000 Apr;7(4):263-74
PMID: 10780926
Abstract
BACKGROUND: Molecular diversity in nature is developed through a combination of genetic and chemical elements. We have developed a method that permits selective manipulation of both these elements in one protein engineering tool. It combines the ability to introduce non-natural …