期刊
ENDOKRYNOLOGIA POLSKA
卷 64, 期 4, 页码 300-304出版社
VIA MEDICA
DOI: 10.5603/EP.2013.0009
关键词
growth hormone; disulphides; structure-activity relationship
资金
- State of Ohio's Eminent Scholar Programme
- AMVETS
- NIH [PO1AG031736]
- Ohio University Baker Award
Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigated the role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be important for biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene, have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH. In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despite decreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study. To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promoting and lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discuss relevant mutations found in patients with growth disorders.
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