Structure/activity relationship of eel calcitonin

Inoue, Akira; Shikano, Mayumi; Komatsu, Yasuhiko; Obata, Junko; Ochiai, Junko; Nishide, Hiroko; Ito, Noriko; Nagao, Hiromasa; Kondo, Kiyoshi; Tunemoto, Daiei; Hemmi, Hiromichi; Numao, Naganori

doi:10.1111/j.1432-1033.1991.tb16321.x

Cited by 10 publications

(4 citation statements)

References 22 publications

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“…The mature peptide is flanked by classic dibasic amino acid processing sites. In the mature peptide, LysK is necessary for the complete expression of biological activity, amino acids 8 to 17 form an amphiphilic alpha helix and form the 3D structure, and the receptor binding region is located between amino acids 24 and 32 (Inoue et al 1991). Comparison of the gene sequence between all species reveals 7 invariant amino acids at positions 1, 4, 5, 6, 7, 28 and 32.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin: characterisation and expression in a teleost fish, Fugu rubripes

Clark

Bendell²,

Power³

et al. 2002

Journal of Molecular Endocrinology

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The present report describes the structure and expression of the calcitonin gene in Fugu rubripes. It is composed of 4 exons and 3 introns. Splicing of exons 1, 2 and 3 generates the calcitonin pre-proprotein, while splicing of exons 1, 2 and 4 generates calcitonin gene-related protein (CGRP). Exons 1 and 2 encoding the signal sequence and the N-terminal peptide are common in both the gene products and this gene organisation has been conserved in human, rat, chicken and salmon. The gene environment around calcitonin in Fugu has been poorly conserved when compared with human, apart from a small gene cluster. The calcitonin gene in Fugu has a widespread tissue distribution but it is most highly expressed in the brain. The abundance of gene expression in the ultimobranchial gland and the pituitary indicates that these are important sites of production and that the peptide is probably secreted into the circulation and/or acts as a paracrine or autocrine controlling factor. Whilst the function of calcitonin in fish is still largely unknown, the distribution described here suggests that one of the potential functions may be as a neuropeptide.

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Section: Discussionmentioning

confidence: 99%

Calcitonin: characterisation and expression in a teleost fish, Fugu rubripes

Clark

Bendell²,

Power³

et al. 2002

Journal of Molecular Endocrinology

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“…However, our detailed observation of a clearly detected medium-range NOE, d AN (i,i ϩ 2), at the Cterminus of eCT indicates that a turn structure exists between the CAH of Arg24 and the NH of Asp26. Furthermore, this NOE connectivity profile in the C-terminal region is also the same in elcatonin, suggesting that this may be the receptor-recognition site which confers specificity, as mentioned by Inoue et al [30]. Therefore, the bend in the C-terminus is thought to play an important role in receptor binding and immunological properties.…”

Section: Resultsmentioning

confidence: 75%

“…Although the fragment Lys11ϪPro32 of eCT showed adenylate cyclase activation, the shorter C-terminal fragment Tyr22ϪPro32 of eCT, which includes the receptor binding region (Arg24ϪPro32), had no effect on adenyl cyclase [29,30]. The resulting structure of eCT has taken on an A-helix at the Nterminal region and a random coil structure at the C-terminal region.…”

Section: Resultsmentioning

confidence: 99%

Conformation analysis of eel calcitonin

Ogawa

Nishimura

Uchiyama

et al. 1998

European Journal of Biochemistry

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The solution structure of eel calcitonin in a mixture of 60% water and 40% trifluoroethanol has been determined in this study by the combined use of 1 H-NMR spectroscopy and distance geometry calculations. 1 H-NMR spectroscopy provided 181 distance constraints, 5 dihedral angle constraints and 14 hydrogen bond constraints. The observed NOEs demonstrated the presence of an amphiphilic A-helix in position Leu4ϪGln20. The seven best converged structures exhibit backbone atomic rmsd of 0.027 nm for the backbone atoms from the averaged coordinate position in the region of Cys1ϪLeu19. In the previous study [Ogawa, K., Nishimura, S., Doi, M., Kyogoku, Y., Hayashi, M. & Kobayashi, Y. (1994) Eur. J. Biochem. 222, 659Ϫ666], the conformation of elcatonin, an analogue of eel calcitonin, was characterized by an amphiphilic A-helix between Thr6 and Thr21 and a turn structure in the first five residues of the N-terminus. The major difference of structure between eel calcitonin and elcatonin exists within the cyclic moiety at the helical N-terminus. Some of the turn structure detected at the N-terminus in elcatonin is not found in eel calcitonin. This is attributed to the difference in the ring formation caused by the disulfide bridge and ethylene bridge. A medium-range NOE, d AN (i,iϩ2), is detected between the CAH of Arg24 and the NH of Asp26, so a turn structure occurs in this segment. This NOE connectivity profile in the C-terminal region is also the same in elcatonin, suggesting that this is important for receptor binding and immunological properties.Keywords : calcitonin; eel calcitonin; amphiphilic A-helix; distance geometry; NMR.Calcitonin is an endogenous peptide produced by the parafollicular cells of the thyroid, parathyroid and thymus glands, which acts principally on bone as a regulator of calcium homeostasis. The therapeutic use of calcitonin is to treat disorders in calcium metabolism involving hypercalcemia, Paget's disease and osteoporosis. Calcitonin has been extracted from various species of animals and primary structures have been determined. Each of them consists of 32 amino acids, containing a disulfide bridge between two cysteine residues in positions 1 and 7 and a proline amide group at the C-terminal end. The physiology and pharmacology of calcitonin have been reviewed by Azria [1].In general, fish calcitonins have more potent biological activities than those of mammals [2]. Many studies on the relationship between structure and biological activity in salmon calcitonin have been carried out. Moe and Kaiser [3] have suggested that an amphiphilic A-helical structure plays an important role in binding to calcitonin receptors. Other structural features such as conformational flexibility have been associated with biological activity as well [4,5]. CD studies have shown that calcitonins have little ordered secondary structure in aqueous solutions. However, the CD spectrum displays a double trough, characteristic of A-helical structure, in the presence of phospholipids or trifluoroethanol [6,7].NMR studies on...

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“…5 To verify this, we investigated human calcitonin (NH 2 -CGNLSTCMLGTYTQDFNKFHTFPQTAIGVGAP-CONH 2 ) (hCT) 27) and salmon calcitonin (NH 2 -CSNL-STCVLGKLSQELHKLQTYPRTNTGSGTP-CONH 2 ) (sCT), 28) in which the region from amino acid number 8 to 22 is the amphipathically a-helical structure, 29) and that from 24 to 32 binds the calcitonin receptor. 30) The cross-spectra of hCT and sCT under three kinds of conditions are shown in Fig. 19, Fig.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the Peptides (Prp106-126, MSI-78A, and Oxaldie 1) with the Same Biological Activity by Discrete Fourier Transform: Toward a Selection Rule in Ligand-Receptor Interaction

Numao

Fujii

Fukazawa

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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Here, we first report a novel method in which the "desired cross-spectrum" of the peptides Prp106-126, MSI-78A, and oxaldie 1 with the same biological activities is obtained by the multiplication of two cross-spectra derived from the RNA sequence and from the cognate amino acid sequence by discrete Fourier transform (DFT), respectively. Based on a well-known method reported previously, we investigated the cross-spectrum by the multiplication of two of three desired cross-spectra. As a result, we found that one prominent peak occurring in the three cross-spectra showed the same frequency when a binary scale was used as a parameter of nucleotide or amino acid in the analysis. Moreover, we examined the relationship between a binary scale and other physicochemical ones. Almost the same results could be reproduced when the absolute electronegativity scale (or the absolute hardness one) was used, but not in the case of the hydrophobic or electron-ion interacting potential scale reported previously. This indicates that either the absolute electronegativity scale (or the absolute hardness one) or a binary scale, or both is very useful in extracting the information desired for various proteins by the present method from the amino acid and the RNA sequence.

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Structure/activity relationship of eel calcitonin

Cited by 10 publications

References 22 publications

Calcitonin: characterisation and expression in a teleost fish, Fugu rubripes

Calcitonin: characterisation and expression in a teleost fish, Fugu rubripes

Conformation analysis of eel calcitonin

Analysis of the Peptides (Prp106-126, MSI-78A, and Oxaldie 1) with the Same Biological Activity by Discrete Fourier Transform: Toward a Selection Rule in Ligand-Receptor Interaction

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