open access

Vol 64, No 4 (2013)
Review article
Published online: 2013-09-04
Submitted: 2013-09-04
Accepted: 2013-09-04
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Significance of the disulphide bonds of human growth hormone

Riia K. Junnila, John J. Kopchick
DOI: 10.5603/EP.2013.0009
·
Endokrynologia Polska 2013;64(4):300-305.

open access

Vol 64, No 4 (2013)
Review article
Published online: 2013-09-04
Submitted: 2013-09-04
Accepted: 2013-09-04

Abstract

Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor 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, despitedecreased 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-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders.

Abstract

Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor 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, despitedecreased 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-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders.
Get Citation

Keywords

growth hormone, disulphides, structure-activity relationship

About this article
Title

Significance of the disulphide bonds of human growth hormone

Journal

Endokrynologia Polska

Issue

Vol 64, No 4 (2013)

Pages

300-305

Published online

2013-09-04

DOI

10.5603/EP.2013.0009

Bibliographic record

Endokrynologia Polska 2013;64(4):300-305.

Keywords

growth hormone
disulphides
structure-activity relationship

Authors

Riia K. Junnila
John J. Kopchick

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