Combined use of proton-proton overhauser enhancements and a distance geometry algorithm for determination of polypeptide conformations. Application to micelle-bound glucagon

Braun, Werner; Bösch, Chris; Brown, L. R.; Gō, Nobuhiro; Wüthrich, Kurt

doi:10.1016/0005-2795(81)90205-1

Cited by 266 publications

(75 citation statements)

References 22 publications

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“…Very strong constraints of 0.22 nm were only used for several CaHi-NHi+ and NHi-CcrHi NOE connectivities. Taking into account of the uniform averaging model [24], the medium-and long-range NOE peaks were classified as strong, medium or weak, and the upper bounds were determined as 0.40, 0.50 and 0.60 nm, respectively. The distance constraints involving methyl and methylene protons were corrected for pseudoatom representation as described by Wuthrich et al [25].…”

Section: Estimation Of Distance Constraintsmentioning

confidence: 99%

Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry

Inooka

Kikuchi

Endo

et al. 1990

European Journal of Biochemistry

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The conformation in solution of porcine brain natriuretic peptide was determined by combined use of NMR spectroscopy and distance geometry. A set of 157 inter-proton-distance constraints was derived from the twodimensional NOE spectra, and further a set of three hydrogen bond constraints was obtained from analysis of the temperature dependence of labile protons. The five structures with minimal violations were selected after performing distance-geometry calculations starting from 40 random initial conformations. The distance-geometry structures were further refined by the use of restrained energy minimization and restrained molecular dynamics. This structure shows a compact conformation with the carboxy-terminal region, Am21 -Tyr26, folded back to the disulfide-linked loop region, Cys4 -Cys20. The characteristics of the conformation determined are as follows: conformations of the three segments interposed by glycine residues, which are Arg7 -Ile12, Serl4 -Leu18 and Cys20 -Arg25, were well defined and the segments Arg7 -Ile12 and Cys20 Porcine brain natriuretic peptide (pBNP) was identified from acid extracts of porcine brain and was classified as a member of the atrial natriuretic peptide (ANP) family [l]. pBNP consists of 26 amino-acid residues and forms a monocyclic structure with a disulfide between Cys4 and Cys2O. The region Cys7 -Tyr28 of human ANP(hANP) exhibits full biological activities, such as natriuretic/diuretic and hypotensive effects. pBNP is distinguished from hANP by possessing six substitutions and one insertion in the corresponding region, Cys4-Tyr26 (Fig. 1) 121. ANP and BNP are both secreted from atrium cordis, so it is supposed that the homeostatic balances of body fluid and blood pressure are under dual regulation involving both ANP and BNP [I].The advances in both NMR methodology and computational techniques over the past few years have made it possible to determine the three-dimensional structures of polypeptides in solution 131. A number of peptide conformations have been resolved by the combined use of two-dimensional (2D) NMR and distance-geometry algorithm [4 -71. ConforCorrespondence to H. Inooka, Wadai 7, Tsukuba, Ibaraki, Japan Abbreviations. BNP, brain natriuretic peptide; pBNP, porcine BNP; ANP, atrial natriuretic peptide; hANP, human ANP; 2D, twodimensional; RMSD, root-mean-square distance; DADAS, distance analysis in dihedral angle space; cHx, cyclohexyl; MeOBzl, pmethoxybenzyl; Pme, pentamethylbenzenesulfonyl; HONB, Nhydroxy-5-norbornene-2,3-dicarboximide; Boc, t-butoxycarbonyl; OcHx, cyclohexyl ester; HOHAHA, 2D homonuclear HartmannHahn spectroscopy; NOESY, 2D nuclear Overhauser enhancement spectroscopy; DQF-COSY, 2D double-quantum-filtered correlated spectroscopy; REM, restrained energy minimization; RMD, restrained molecular dynamics. 300-42mational studies of hANP using 2D NMR techniques have been reported [8 -111. A defined conformation could not be found in most of these studies due to the flexibility of the peptide molecule in solution. Kobayashi et al. reported a defin...

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Section: Estimation Of Distance Constraintsmentioning

confidence: 99%

Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry

Inooka

Kikuchi

Endo

et al. 1990

European Journal of Biochemistry

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“…In addition to the backbone arrangement in Fig.7, NOEs with side-chain protons allow further characterization of this structural region. Proximity within about 0.5 nm [54] to the tyrosine-25 ring is indicated for the tyrosine-59 ring, the isoleucine-46 methyl groups, the tryptophan-I 5 ring, and the methionine methyl at 1.99 ppm. The NOE data are thus consistent with the ring-current shifts [50] observed for isoleucine-46 and the titration shifts observed between pH 9 and 11 for isoleucine-46, tryptophan-14, and the methionine methyl group at 1.99 ppm (Fig.…”

Section: Sequential Assignments Qf Polypeptide Backbone Resonances Anmentioning

confidence: 99%

¹H Nuclear‐Magnetic‐Resonance Studies of the Conformation of Cardiotoxin V^II2 from Naja mossambica mossambica

Steinmetz

Moonen

Kumar

et al. 1981

European Journal of Biochemistry

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The membrane toxin V"2 from the venom of Naja mossamhica niossambica was investigated in aqueous solution by one-dimensional and two-dimensional high-resolution nuclear magnetic resonance (NMR) techniques at 360 MHz. The spectral characterization included identification of the complete spin systems for several amino acid residues, nuclear Overhauser effect measurements, the use of chemically induced dynamic nuclear polarization and studies of the pH dependence of the N M R spectrum. Data from homologous toxins, in particular direct lytic factor 12B from Haemachatus haenzachatus, were used to establish assignments of aromatic and methyl proton resonances. From these experiments a short, triple-stranded fragment of antiparallel p structure could be determined, which includes the residues 23 -27, 43 -46 and 60 -62. Furthermore, the nuclear Overhauser effect measurements indicate close proximity in the protein conformation of the aromatic rings of Trp-14, Tyr-25 and Tyr-59, and the side chain of Ile-46.Keen interest in the toxins from the venoms of snakes belonging to the family Elapidae (cobra, coral snake, sea snake, etc.) has generated an extensive literature [l -31. Three classes of toxins are usually distinguished: long neurotoxins, short neurotoxins, and membrane toxins. These three classes form a group of homologous proteins with 71 -74, 60 -62, and 60-62 amino acid residues, respectively, arranged in a single polypeptide chain. If one excludes an extra disulfide bridge in the long neurotoxins, all of the approximately 80 toxins sequenced so far have four disulfide bridges linking half-cysteine residues which have homologous locations in the sequence. In addition seven other amino acid residues are located at homologous positions. Within a class or subclass of toxins, homology is even more extensive and can be as high as 60-70 % (e.g. membrane toxins from the genus Nuja). In spite of the extensive homology, there are pronounced differences in the mode of action of the different types of toxins. Neurotoxins bind to a protein receptor at the post-synaptic level and block acetylcholine reception [4]. The action of membrane'toxins results in a variety of effects including hemolysis, cytotoxieity, depolarization of excitable membrane and modulation of membranal enzyme activity [2,5]. This varied phenomenology has produced a profusion of trivial names such as cardiotoxin, cytotoxin, and direct lytic factor. A common trait of the actions of the different membrane toxins at the cellular level appears to be binding to the cell membrane with disturbance of its organization and function [5 -71.A variety of approaches have been used to investigate the spatial structures of snake neurotoxins and cardiotoxins [I, 21. These have included structure-activity modelling studies employing in part Chou-Fasman-type predictions [8 -lo], Abbreviations. CD, circular dichroism; 6, chemical shift; lytic factor 12B, direct lytic factor 12B from Haemachatus haemachaius; NMR, nuclear magnetic resonance; NOE, nuclear Overhauser effect; ppi...

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“…The first NMR protein (peptide) structure was determined in 1981 using protocols and techniques largely developed by Kurt Wuthrich and co-workers [18]. This work was recognized in 2002 when he was awarded the Nobel Prize in chemistry.…”

Section: Nmr Basicsmentioning

confidence: 99%

NMR Spectroscopy and Protein Structure Determination: Applications to Drug Discovery and Development

Wishart

2005

CPB

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Recent technological advances in NMR methods and instrumentation are having a significant impact in structural biology. These innovations are also impacting pharmaceutical biotechnology as it is now possible to use NMR spectroscopy to rapidly characterize a growing number of prospective protein drugs and protein drug targets. This review provides a general summary of how solution-state NMR can be used to determine protein structures. It also focuses on exploring how advances in solution state NMR are changing the way in which protein structures can be determined and protein-ligand interactions can be characterized. Recent innovations in protein sample preparation, in instrumentation and data collection, in spectral assignment and in structure generation are highlighted. The impact of solution-state NMR on pharmaceutical biotechnology is also discussed, with a special emphasis on describing how NMR has been used to study a number of pharmaceutically important proteins and how NMR is currently being used to rapidly screen and to map the binding sites of small molecules to a range of protein targets.

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Combined use of proton-proton overhauser enhancements and a distance geometry algorithm for determination of polypeptide conformations. Application to micelle-bound glucagon

Cited by 266 publications

References 22 publications

Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry

Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry

¹H Nuclear‐Magnetic‐Resonance Studies of the Conformation of Cardiotoxin V^II2 from Naja mossambica mossambica

NMR Spectroscopy and Protein Structure Determination: Applications to Drug Discovery and Development

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Combined use of proton-proton overhauser enhancements and a distance geometry algorithm for determination of polypeptide conformations. Application to micelle-bound glucagon

Cited by 266 publications

References 22 publications

Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry

Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry

1H Nuclear‐Magnetic‐Resonance Studies of the Conformation of Cardiotoxin VII2 from Naja mossambica mossambica

NMR Spectroscopy and Protein Structure Determination: Applications to Drug Discovery and Development

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¹H Nuclear‐Magnetic‐Resonance Studies of the Conformation of Cardiotoxin V^II2 from Naja mossambica mossambica