Does the solid‐state structure of endothelin‐1 provide insights concerning the solution‐state conformational equilibrium?

Lee, Gregory M.; Chen, Chinpan; Marschner, T.; Andersen, Niels H.

doi:10.1016/0014-5793(94)01153-2

Cited by 9 publications

(15 citation statements)

References 33 publications

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“…The lack of an upfield Ha shift at Leu 12 is attributed to a ring current effect due to the Phe 15 sidechain (vide infra). Plots of inter/intra-Ha -HN NOE ratios (a i N iþ1 /a i N i , Lee et al, 1994) for hAM ( Fig. S6, Supplementary data are available at PEDS online), and prAM do not show any interruption in the helical c values through the 6 -20 residue span.…”

Section: Nmr Parameter Comparisons In Aqueous Hfipmentioning

confidence: 99%

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Solution state structures of human pancreatic amylin and pramlintide

Cort

Liu

Lee

et al. 2009

Protein Engineering, Design and Selection

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We have employed pramlintide (prAM) as a surrogate for hAM in CD and NMR studies of the conformational preferences of the N-terminal portion of the structure in media which do not provide long-lived monomeric solutions of hAM due to its rapid conversion to preamyloid beta aggregate states. Direct comparison of hAM and prAM could be made under helix-formation-favoring conditions. On the basis of CD and NMR studies: (i) the Cys(2)-Cys(7) loop conformation has a short-span of helix (Ala(5)-Cys(7)); (ii) the extent to which this helix propagates further into the sequence is medium-dependent; a helix from Ala(5) through Ser(20) (with end fraying from His(18) onward) is observed in aqueous fluoroalcohol media; (iii) in 12+ vol.% HFIP, the amyloidogenic region of hAM forms a second helical domain (Phe(23)-Ser(29)); (iv) the two helical regions of hAM do not have any specific geometric relationship as they are connected by a flexible loop that takes different conformations and (v) although the extreme C-terminus is essential for bioactivity, it is found to be extensively randomized with conformer interconversions occurring at a much faster rate than that is observed in the remainder of the peptide sequence. Two NMR-derived structures of the 1-22 sequence fragment of hAM have been derived. The work also serves to illustrate improved methods for the NMR characterization of helices. A detailed quantitative analysis of the NOE intensities observed in aqueous HFIP revealed alternative conformations in the C-terminal portion of the common amylin helix, a region that is known to be involved in the biorecognition phenomena leading to amyloidogenesis. Even though the SNN sequence appears to be a flexible loop, the chemical shifts (and changes induced upon helix structuring) suggest some interactions between the loop and the amyloidogenic segment of hAM that occur on partial helix formation.

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Section: Nmr Parameter Comparisons In Aqueous Hfipmentioning

confidence: 99%

“…Sequence histograms of inter-/intra-residue Ha -HN NOE ratios are calculated and displayed as described by Lee et al (1994). Structuring shift comparisons, as sequence plots of CSDs, CSD…”

Section: Nmr Spectroscopy and Analysismentioning

confidence: 99%

Solution state structures of human pancreatic amylin and pramlintide

Cort

Liu

Lee

et al. 2009

Protein Engineering, Design and Selection

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“…Solution structure determination of endothelin-1 by NMR has been reported as being characterized by an alpha-helical conformation, Lys9-His16, and by residues Ser5-Asp8 forming a type I beta-turn (21). It has been shown by chemical shift data that the helical conformational preference of endothelins in aqueous solutions is not altered by the addition of organic solvents such as acetonitrile (22).…”

Section: Discussionmentioning

confidence: 98%

An Automated High-Performance Liquid Chromatography Fluorescence Method for the Analyses of Endothelins in Plasma Samples

Kumarathasan

Goegan

Vincent

2001

Analytical Biochemistry

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“…Whereas endothelin-3 also aggregates in aqueous solution [28], no aggregation data have hitherto been reported on endothelin-2. Comparisons between structures of endothelin-1 calculated from data acquired in different solvents are published [25,36,37]. Discrepancies between the calculated structures are in part attributed to the use of different solvent systems.…”

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confidence: 99%

“…tional deviations between the endothelin peptides reflect real differences between the solution conformations and should be due to variation in primary structure [28]. Moreover, a comparative study reports that the crystal structure of endothelin-1 shows marked discrepancies from any endothelin solution structure [36].…”

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The solution structure of human endothelin‐2 a ¹H‐NMR and CD study

Arvidsson¹,

Nemoto²,

Mitsui³

et al. 1998

European Journal of Biochemistry

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The solution structure of the vasoactive endogenous 21-amino-acid human endothelin-2 has been determined by NMR and CD techniques, in a mixed solvent of 100 mM aqueous acetic acid and 25% (by vol.) 1,1,1,3,3,3-hexafluoro-2-propanol. From NMR-derived restraints on upper limit distances and dihedral angles, distance geometry structures were calculated using the program DADAS90, and refined by simulated annealing in X-PLOR. The structure of endothelin-2 consists of an A-helix of residues 9 to 17, orientated anti-parallel to a short β-strand of residues 1 to 3, linked together by a possible β-turn type I of residues 5Ϫ8. These secondary structural elements are stabilised and positioned by two disulphide bonds between residues 1 and 15, and 3 and 11, respectively. The average root mean square deviation over residues 1Ϫ17 of 15 accepted low-energy conformers chosen to reflect the solution structure of endothelin-2, was 0.73 Å for the backbone and 1.41 Å for all heavy atoms. The data on endothelin-2 will be discussed and compared with what has been published on other endothelin/sarafotoxin peptides.Keywords : endothelin-2; NMR; circular dichroism ; solution structure ; helix.Endothelin-1 was first isolated from porcine aortic endothelial cells [1]. The human genes encoding this peptide and two isoforms, endothelin-2 and endothelin-3, have been encountered and cloned [2]. From analysis of a mouse genome another peptide called vasoactive intestinal contractor (VIC) was identified [3]. These four mammalian peptides are strongly homologous ( Fig. 1). Moreover, they have pronounced sequence similarities with the snake venom sarafotoxins [4] and Bibrotoxin [5]. For this reason they have been suggested to form an endothelin/sarafotoxin peptide family. These peptides have 21 residues and two disulphide bonds connecting residues 1 and 15, and 3 and 11, respectively. They are also noted for evoking similar biological actions [6].The endothelin peptides were first characterised as being the most potent constrictors of smooth muscle. They are now known to produce a variety of pharmacological effects in various vascular and non-vascular tissues and to show numerous activities in the central and peripheral nervous systems. They have been linked to regulation of blood flow and to a number of diseases such as vasospasm, hypertension, myocardial infarction, arteriosclerosis and renal failure [7]. The role as a vasoconstrictor has however been questioned after a finding that blood pressure of transgenic 'knock-out' mice with only one copy of the gene, is somewhat raised, rather than lowered as was expected [8]. Disruption of both copies of the gene results in an embryonic lethal phenotype with malformed craniofacial organs [8].Two G-protein-coupled endothelin receptors have been characterised and cloned in mammalian species, ET A and ETB [9,Correspondence to H. Nakanishi, Biomolecular Chemistry Laboratory, Department of Biomolecules, National Institute of Bioscience and Human-Technology (NIBH), 1-1 Higashi, Tsukuba, Ibaraki, Japan 305-8...

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Does the solid‐state structure of endothelin‐1 provide insights concerning the solution‐state conformational equilibrium?

Cited by 9 publications

References 33 publications

Solution state structures of human pancreatic amylin and pramlintide

Solution state structures of human pancreatic amylin and pramlintide

An Automated High-Performance Liquid Chromatography Fluorescence Method for the Analyses of Endothelins in Plasma Samples

The solution structure of human endothelin‐2 a ¹H‐NMR and CD study

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Does the solid‐state structure of endothelin‐1 provide insights concerning the solution‐state conformational equilibrium?

Cited by 9 publications

References 33 publications

Solution state structures of human pancreatic amylin and pramlintide

Solution state structures of human pancreatic amylin and pramlintide

An Automated High-Performance Liquid Chromatography Fluorescence Method for the Analyses of Endothelins in Plasma Samples

The solution structure of human endothelin‐2 a 1H‐NMR and CD study

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The solution structure of human endothelin‐2 a ¹H‐NMR and CD study