A theoretical study of the structure of parathyroid hormone.

Zull, James E.; Lev, Naomi B.

doi:10.1073/pnas.77.7.3791

Cited by 34 publications

(11 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondary structure predicted by the Chou-Fasman algorithm was then fitted into the three dimensional structure. A semi-empirical model derived by the use of various prediction schemes in combination with available chemical data (Zull and Lev, 1980) showed the same global features.…”

Section: Introductionmentioning

confidence: 96%

Structure of Recombinant Human Parathyroid Hormone in Solution Using Multidimensional NMR Spectroscopy

Gronwald¹,

Schomburg²,

Harder³

et al. 1996

Biological Chemistry Hoppe-Seyler

View full text Add to dashboard Cite

The solution structure of human parathyroid hormone, in the form of recombinant prolyl-hPTH(1-84), has been investigated by multidimensional NMR spectroscopy under conditions (aqueous trifluoroethanol) which favour the structured-state of the protein. Spin systems were identified from 3D 1H DQF (double-quantum filtered)-COSY and TOCSY spectra and sequence-specific assignments were from 2D 1H phase-sensitive NOESY spectra. Signal overlap was resolved in a 3D-NOESY-TOCSY spectrum and assignments were confirmed with 2D NOESY-15N-HMQC (heteronuclear multiple-quantum coherence) spectra taken of a sample universally labeled with 15N. A satisfactory set of final structures was calculated from the quantitative NOE data using restrained molecular dynamics and energy minimization calculations. The N-terminus is dominated by three, well defined helices between Ser-3 to Asn-10, Ser-17 to Lys-27 and Asp-30 to Leu-37, while the most significant structural features in the C-terminus are a short, less-well defined helix between Asn-57 to Ser-62 and a series of loose turns. These two terminal units are joined by an unstructured mid-region. The molecule shows a tendency towards tertiary structure, defined by a number of long-range NOEs. A detailed RMS deviation analysis allowed the final refined structures to be classified into a limited ensemble of stable conformations that reflect the inherent flexibility of the hormone in solution.

show abstract

Section: Introductionmentioning

confidence: 96%

Structure of Recombinant Human Parathyroid Hormone in Solution Using Multidimensional NMR Spectroscopy

Gronwald¹,

Schomburg²,

Harder³

et al. 1996

Biological Chemistry Hoppe-Seyler

View full text Add to dashboard Cite

show abstract

“…1). 2,3 Dark field electron microscopy has also shown the presence of N-and C-terminal domains in the PTH molecule. "…”

Section: The Strucfure Of Intacf Human Pthmentioning

confidence: 99%

The Measurement of Parathyroid Hormone

Wood

1992

Ann Clin Biochem

View full text Add to dashboard Cite

Additional key phrases: biologically inactive PTH fragments; limitations of PTH; RIAs and bioassays; two-site immunometric assays for intact PTHAlthough the first radioimmunoassay (RIA) for PTH was published in 1963 1 until recently the measurement and interpretation of serum PTH levels has been difficult and this has limited the value of PTH assays in the investigation of hypercalcaemia. This report deals with the problems and limitations of PTH RIAs and bioassays and emphasizes the advantages of newer two-site immunometric intact PTH methods. The factors influencing the interpretation of intact PTH results and the characteristics of the available methods are reviewed.

show abstract

“…model, different in specific details but with the same global features, was derived semiempirically from various prediction schemes combined with available chemical data (Zull & Lev, 1980). It is only recently, with the possibility of using highfield NMR spectroscopy, that the acceptability of such models can be probed.…”

mentioning

confidence: 99%

The Structure Of Human Parathyroid Hormone From a Study of Fragments in Solution Using 1H NMR Spectroscopy and Its Biological Implications

Wray

Federau²,

Gronwald³

et al. 1994

Biochemistry

View full text Add to dashboard Cite

In order to gain insight into the structure of human parathyroid hormone (hPTH), four fragments [hPTH(1-34), hPTH(18-48), hPTH(28-48), and hPTH(53-84)], which cover all regions of the intact hormone, have been investigated by CD and NMR spectroscopy in combination with distance geometry, and restrained molecular dynamics and energy minimization calculations, under a variety of solution conditions. Significantly, all fragments showed little propensity to form stable structures in aqueous solution alone, and it was only on the addition of trifluoroethanol (TFE) that defined structural features were observed. In an extension of earlier work [Klaus et al. (1991) Biochemistry 30, 6936-6942], hPTH(1-34) in 70% trifluoroethanol (TFE) showed two helices that were longer than in 10% TFE, but essentially showed the same characteristics. Although overlap in the 1H NMR spectra prevented the determination of quantitative NOE data for residues 26-30, the combination of the alpha-proton chemical shift data and quantitative NOE data indicated the helices extend from residues 3 to 13 and 15 to 29. No evidence was found for interaction of the two helical regions. The nature and extent of this second helix in the intact hormone were better defined from the data for hPTH(18-48). Under limiting solution conditions, where the fragment assumed its maximum helical content, a well-defined helix was observed between residues 21 and 38 with a possible discontinuity between Leu-28 and Gln-29. There was little evidence of any form of secondary structure between Gly-38 and the terminus of this fragment, Ser-48. In keeping with this result, the shorter fragment, hPTH(28-48), showed little evidence of stable secondary structure on addition of TFE. From the alpha-proton chemical shifts residues 23-27 appeared to sustain helical structure more readily than the rest of molecule under all solution regimes in both hPTH(1-34) and hPTH(18-48). In contrast to the other two longer fragments hPTH(53-84) showed little propensity for helical secondary structure even at the highest TFE concentrations. However, there was evidence that the molecule did adopt a defined three-dimensional structure. Various long-range NOE's were observed in 10% TFE that allowed the calculation of an open tertiary structure consisting of an initial series of turns surrounded by a loop structure of several loose turns.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

A theoretical study of the structure of parathyroid hormone.

Cited by 34 publications

References 25 publications

Structure of Recombinant Human Parathyroid Hormone in Solution Using Multidimensional NMR Spectroscopy

Structure of Recombinant Human Parathyroid Hormone in Solution Using Multidimensional NMR Spectroscopy

The Measurement of Parathyroid Hormone

The Structure Of Human Parathyroid Hormone From a Study of Fragments in Solution Using 1H NMR Spectroscopy and Its Biological Implications

Contact Info

Product

Resources

About