Does the Most Stable Conformation Correlate With the Highest Biological Potency? A Case Study of Human Transforming Growth Factor Type Alpha,

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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.

Author(s):
Shen, Zhiyi ; Ke, Xiaohong ; Zhang, Jing-wen ; Tam, James P.
Author Organization(s):
ROCKEFELLER UNIV NEW YORK
Supplementary Note:
This article is from 'Peptides. Chemistry and Biology: Proceedings of the American Peptide Symposium (12th) Held in Cambridge, Massachusetts on 16-21 June 1991', AD-A256 113, p217-218.
Pagination:
0002

Security Markings

DOCUMENT & CONTEXTUAL SUMMARY

Distribution:
Approved For Public Release

RECORD

Collection: TR
Identifying Numbers
Monitor Series:
USAMRDC
 Subject Terms
Communities of Interest:
No COI(s) Identified
Descriptor(s):
*PROTEINS, *STABILITY, *POTENCY, *PEPTIDE HYDROLASES, *HORMONES, CORRELATION, BIOLOGY, HUMANS, RECEPTOR SITES(PHYSIOLOGY), STRUCTURES, MODELS, HYDROGEN, GROWTH(PHYSIOLOGY), IMIDAZOLES, HISTIDINE, ROTATION, CHEMICAL BONDS
Field(s)/Group(s):
Biochemistry, Biology, Anatomy and Physiology
Keyword(s):
Component Reports, Conformation correlate, Biological potency, *TGF(Transforming Growth Factor Type Alpha), Alterations, Imidazoyl side chain
Report Date:
1992 Jan 01