Accession Number : ADP008364
Title : Does the Most Stable Conformation Correlate With the Highest Biological Potency? A Case Study of Human Transforming Growth Factor Type Alpha,
Corporate Author : ROCKEFELLER UNIV NEW YORK
Personal Author(s) : Shen, Zhiyi ; Ke, Xiaohong ; Zhang, Jing-Wen ; Tam, James P.
Report Date : 1992
Pagination or Media Count : 2
Abstract : Much has been learned regarding the conformational stability of proteins, particularly proteases. However, little is known about protein growth factors and hormones which differ in their modes of biological function. These protein hormones bind to specific receptors and the relationship between structural alterations leading to different conformational stability and biological activity have seldomly been addressed. For such a purpose, the 50-residue human transforming growth factor type alpha (TGF alpha) is particularly suitable model. Our previous studies using an alanine scan have shown that none of the His residues are involved in the receptor-contact functions. To delineate the roles of aromatic, hydrogen donor or acceptor contribution of each imidazoyl side chain in the conformational stability, each histidine was substituted individually by Phe Asn and Asp. Their conformational stability was determined from thermal unfolding by CD.
Descriptors : *PROTEINS, *STABILITY, *POTENCY, *PEPTIDE HYDROLASES, *HORMONES, CORRELATION, BIOLOGY, HUMANS, RECEPTOR SITES(PHYSIOLOGY), STRUCTURES, MODELS, HYDROGEN, GROWTH(PHYSIOLOGY), IMIDAZOLES, HISTIDINE, ROTATION, CHEMICAL BONDS.
Subject Categories : Biochemistry
Anatomy and Physiology
Distribution Statement : APPROVED FOR PUBLIC RELEASE