|1hgu, resolution 2.50Å ()|
HUMAN GROWTH HORMONE
The thermal denaturation of recombinant human growth hormone (rhGH) was studied by differential scanning calorimetry and circular dichroism spectroscopy (CD). The thermal unfolding is reversible only below pH 3.5, and under these conditions a single two-state transition was observed between 0 and 100 degrees C. The magnitudes of the deltaH and deltaCp of this transition indicate that it corresponds to a partial unfolding of rhGH. This is also supported by CD data, which show that significant secondary structure remains after the unfolding. Above pH 3.5 the thermal denaturation is irreversible due to the aggregation of rhGH upon unfolding. This aggregation is prevented in aqueous solutions of alcohols such as n-propanol, 2-propanol, or 1,2-propanediol (propylene glycol), which suggests that the self-association of rhGH is caused by hydrophobic interactions. In addition, it was found that the native state of rhGH is stable in relatively high concentrations of propylene glycol (up to 45% v/v at pH 7-8 or 30% at pH 3) and that under these conditions the thermal unfolding is cooperative and corresponds to a transition from the native state to a partially folded state, as observed at acidic pH in the absence of alcohols. In higher concentrations of propylene glycol, the tertiary structure of rhGH is disrupted and the cooperativity of the unfolding decreases. Moreover, the CD and DSC data indicate that a partially folded intermediate with essentially native secondary structure and disordered tertiary structure becomes significantly populated in 70-80% propylene glycol.
Thermodynamic characterization of an intermediate state of human growth hormone., Gomez-Orellana I, Variano B, Miura-Fraboni J, Milstein S, Paton DR, Protein Sci. 1998 Jun;7(6):1352-8. PMID:009655339
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[SOMA_HUMAN] Defects in GH1 are a cause of growth hormone deficiency isolated type 1A (IGHD1A) [MIM:262400]; also known as pituitary dwarfism I. IGHD1A is an autosomal recessive deficiency of GH which causes short stature. IGHD1A patients have an absence of GH with severe dwarfism and often develop anti-GH antibodies when given exogenous GH. Defects in GH1 are a cause of growth hormone deficiency isolated type 1B (IGHD1B) [MIM:612781]; also known as dwarfism of Sindh. IGHD1B is an autosomal recessive deficiency of GH which causes short stature. IGHD1B patients have low but detectable levels of GH. Dwarfism is less severe than in IGHD1A and patients usually respond well to exogenous GH. Defects in GH1 are the cause of Kowarski syndrome (KWKS) [MIM:262650]; also known as pituitary dwarfism VI. Defects in GH1 are a cause of growth hormone deficiency isolated type 2 (IGHD2) [MIM:173100]. IGHD2 is an autosomal dominant deficiency of GH which causes short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy.
[SOMA_HUMAN] Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
About this Structure
1hgu is a 1 chain structure with sequence from Homo sapiens. The April 2004 RCSB PDB Molecule of the Month feature on Growth Hormone by Shuchismita Dutta and David S. Goodsell is 10.2210/rcsb_pdb/mom_2004_4. Full crystallographic information is available from OCA.
- Gomez-Orellana I, Variano B, Miura-Fraboni J, Milstein S, Paton DR. Thermodynamic characterization of an intermediate state of human growth hormone. Protein Sci. 1998 Jun;7(6):1352-8. PMID:9655339 doi:10.1002/pro.5560070611
- Kasimova MR, Kristensen SM, Howe PW, Christensen T, Matthiesen F, Petersen J, Sorensen HH, Led JJ. NMR studies of the backbone flexibility and structure of human growth hormone: a comparison of high and low pH conformations. J Mol Biol. 2002 May 3;318(3):679-95. PMID:12054815 doi:10.1016/S0022-2836(02)00137-7
- Hill EE, Morea V, Chothia C. Sequence conservation in families whose members have little or no sequence similarity: the four-helical cytokines and cytochromes. J Mol Biol. 2002 Sep 6;322(1):205-33. PMID:12215425
- Duda KM, Brooks CL. Identification of residues outside the two binding sites that are critical for activation of the lactogenic activity of human growth hormone. J Biol Chem. 2003 Jun 20;278(25):22734-9. Epub 2003 Apr 7. PMID:12682073 doi:10.1074/jbc.M212550200
- ↑ Igarashi Y, Ogawa M, Kamijo T, Iwatani N, Nishi Y, Kohno H, Masumura T, Koga J. A new mutation causing inherited growth hormone deficiency: a compound heterozygote of a 6.7 kb deletion and a two base deletion in the third exon of the GH-1 gene. Hum Mol Genet. 1993 Jul;2(7):1073-4. PMID:8364549
- ↑ Takahashi Y, Kaji H, Okimura Y, Goji K, Abe H, Chihara K. Brief report: short stature caused by a mutant growth hormone. N Engl J Med. 1996 Feb 15;334(7):432-6. PMID:8552145 doi:http://dx.doi.org/10.1056/NEJM199602153340704
- ↑ Takahashi Y, Shirono H, Arisaka O, Takahashi K, Yagi T, Koga J, Kaji H, Okimura Y, Abe H, Tanaka T, Chihara K. Biologically inactive growth hormone caused by an amino acid substitution. J Clin Invest. 1997 Sep 1;100(5):1159-65. PMID:9276733 doi:10.1172/JCI119627
- ↑ Petkovic V, Besson A, Thevis M, Lochmatter D, Eble A, Fluck CE, Mullis PE. Evaluation of the biological activity of a growth hormone (GH) mutant (R77C) and its impact on GH responsiveness and stature. J Clin Endocrinol Metab. 2007 Aug;92(8):2893-901. Epub 2007 May 22. PMID:17519310 doi:10.1210/jc.2006-2238