High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis.
The overall folding of these mutant proteins was indistinguishable from that of the wild-type hGH, as determined by strong cross-reactivities with seven different conformationally sensitive monoclonal antibodies.
Phage display for selection of novel binding peptides.
Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule.
- B. Cunningham, M. Ultsch, A. D. de Vos, M. Mulkerrin, K. Clauser, J. Wells
- Biology, ChemistryScience
- 8 November 1991
Human growth hormone (hGH) forms a 1:2 complex with the extracellular domain of its receptor-binding protein (hGHbp) as studied by crystallization, size exclusion chromatography, calorimetry, and a…
Rational design of potent antagonists to the human growth hormone receptor.
- G. Fuh, B. Cunningham, R. Fukunaga, S. Nagata, D. Goeddel, J. Wells
- Biology, MedicineScience
- 19 June 1992
Inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation and could be useful for treating clinical conditions of hGH excess, such as acromegaly.
Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site.
- Y. Muller, B. Li, H. Christinger, J. Wells, B. Cunningham, A. D. de Vos
- Biology, ChemistryProceedings of the National Academy of Sciences…
- 8 July 1997
Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended, and functional analysis of the binding epitopes for two receptor-blocking antibodies reveal different binding determinants near each of the KDR binding hot spots.
Comparison of a structural and a functional epitope.
The study shows that only one-quarter of the side-chains buried at the interface can account for the majority of the binding energy, and the fact that the functional binding epitope is much smaller than the structural epitope suggests it may be possible to design smaller hormone mimics.
Small-Molecule Inhibition of TNF-α
A small-molecule inhibitor of tumor necrosis factor α (TNF-α) that promotes subunit disassembly of this trimeric cytokine family member and forms a complex with a dimer of TNF- α subunits is identified.
Small-molecule inhibition of TNF-alpha.
A structure solved by x-ray crystallography reveals that a single compound molecule displaces a subunit of the trimer to form a complex with a dimer of TNF-alpha subunits.
Requirements for Binding and Signaling of the Kinase Domain Receptor for Vascular Endothelial Growth Factor*
- G. Fuh, B. Li, C. Crowley, B. Cunningham, J. Wells
- Biology, ChemistryJournal of Biological Chemistry
- 1 May 1998
Based upon structure-function studies and a mechanism in which receptor dimerization is critical for signaling, a receptor antagonist in the form of a heterodimer of VEGF that contained one functional and one non-functional site is constructed to establish a functional foundation for the design of V EGF analogs, mimics, and antagonists.
Dimerization of human growth hormone by zinc.
The Zn(2+)-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl and may be important for storage of hGH in secretory granules.