Intramolecular proton nuclear Overhauser effect study of the solution conformation of valinomycin in dimethyl sulfoxide

Glickson, Jerry D.; Gordon, Sidney L.; Pitner, T. Phil; Agresti, D. G.; Walter, Roderich

doi:10.1021/bi00671a007

Cited by 70 publications

(29 citation statements)

References 33 publications

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“…Stern, Gibbons & Craig, 1968;Ovchinnikov et al 1970;Urry & Ohnishi, 1974;Wiithrich, Grathwohl & Schwyzer, 1974;Kopple, Go & Pilipauskas, 1975;Howard et al 1975;Stimson, Zimmerman & Scheraga, 1977). Recently, the applicability of the technique has been extended by use of the nuclear Overhauser effect to distinguish between various types of bend conformations (Khaled & Urry, 1976) and, in general, to obtain information about the dihedral angle ijr, for rotation about the C a -C bond, and about side-chain conformation (Glickson et al 1976;Leach, Nemethy & Scheraga, 1977). However, the application of NMR to the study of globular proteins is much more difficult because of overlapping of the resonances from the many protons of the protein molecule.…”

Section: The Exposure Of Residues To the Solventmentioning

confidence: 99%

Protein folding

Némethy

Scheraga

1977

Quart. Rev. Biophys.

296

125

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This review describes recent advances in studies on the stabilities of the three-dimensional structures of proteins and on the processes leading to the formation of these structures. The term ‘protein folding’ will be used here to denote the process of the conversion of an open polypeptide chain into the unique three-dimensional conformation of the native protein. Experimental and theoretical aspects of protein folding have been reviewed by anfinsen & Scheraga (1975). In the present article, we emphasize advances made since the writing of that review, together with a brief summary of the background of recent studies.

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Section: The Exposure Of Residues To the Solventmentioning

confidence: 99%

Protein folding

Némethy

Scheraga

1977

Quart. Rev. Biophys.

296

125

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“…Most of the solution proton ( 1 H) NMR studies of drug-membrane interactions utilize detergent micelles or organic solvents instead of bilayer membranes (22,23). However, the packing of phospholipids in micelles is remarkably different from that in a bilayer (24).…”

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confidence: 99%

Membrane Conformations and Their Relation to Cytotoxicity of Asimicin and Its Analogues

et al. 1998

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Certain plant species belonging to the family Annonaceae produce Annonaceous acetogenins, which are a unique class of long-chain fatty acid derivatives with potent cytotoxicity. Putative protein targets of the acetogenins are membrane-associated proteins, including complex I. Asimicin and its analogues constitute a class of Annonaceous acetogenins containing two tetrahydrofuran (THF) rings with hydrocarbon chains tethered to each ring; an alpha,beta-unsaturated gamma-lactone ring is terminal to one of the alkyl chains. The compounds examined in this study differ in the length of the alkyl chain between the THF rings and the lactone ring. The positions of both the THF and the lactone rings within liposomal membranes were determined by proton (1H) nuclear magnetic resonance spectroscopy. The depth of membrane penetration of acetogenins, coupled to membrane diffusion, controls the conformation of acetogenins as they diffuse to an active site. Based on 1H intermolecular nuclear Overhauser effects (NOEs), the THF rings of all acetogenins studied reside near the polar interfacial head group region of the DMPC. This was corroborated by 1H two-dimensional NOE spectroscopy and differential scanning calorimetry studies. The 1H difference NOE spectra indicated that the lactone rings of asimicin and parviflorin, the latter of which has two fewer carbons in its alkyl chain, are located below the glycerol backbone in the membrane. In contrast with asimicin and parviflorin, the lactone ring of longimicin B, an asimicin analogue with an alkyl chain four carbons shorter, resides close to the midplane in the membrane. This was corroborated by manganese-induced broadening studies. Since the THF rings are located near the center of the acetogenin molecules and the lactone ring is terminal to a long alkyl chain, these observations indicate that an asimicin-type acetogenin can be in either sickle-shaped or U-shaped conformations, depending on the length of the alkyl chain between the THF rings and the lactone ring. Interestingly, longimicin B does not exhibit significant cytotoxicity, but parviflorin is as cytotoxic as asimicin. The cytotoxicity of the asimicin-type of acetogenins would seem to be strongly related to the membrane conformation. This is the first report elucidating the conformation of Annonaceous acetogenins in membranes.

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“…These factors have meant that scalar relaxation effects have been considered unlikely to be apparent in NOE experiments performed with modern high-field spectrometers. [16] We believe scalar cross-relaxation of the first kind has not previously been reported as being observed in 2D NOESY spectra and, it appears, the effect has only rarely been detected experimentally. The clearest example of this appears to be the work of Fukumi et al [17] over forty years ago in which negative NOEs were observed between the coupled CH-OH protons of methanol and ethanol and attributed to scalar relaxation.…”

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confidence: 76%

Anomalous Nuclear Overhauser Effects in Carbon‐Substituted Aziridines: Scalar Cross‐Relaxation of the First Kind

et al. 2015

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Anomalous NOESY cross-peaks that cannot be explained by dipolar cross-relaxation or chemical exchange are described for carbon-substituted aziridines. The origin of these is identified as scalar cross-relaxation of the first kind, as demonstrated by a complete theoretical description of this relaxation process and by computational simulation of the NOESY spectra. It is shown that this process relies on the stochastic modulation of J-coupling by conformational transitions, which in the case of aziridines arise from inversion at the nitrogen center. The observation of scalar cross-relaxation between protons does not appear to have been previously reported for NOESY spectra. Conventional analysis would have assigned the cross-peaks as being indicative of a chemical exchange process occurring between correlated spins, were it not for the fact that the pairs of nuclei displaying them cannot undergo such exchange.Among the powerful NMR structure and conformation elucidation techniques, [1] nuclear Overhauser effect (NOE) experiments play a central role because they map the spatial proximity of neighboring spins.[2] The experimental techniques used to observe magnetization transport due to NOEs (NOE spectroscopy or NOESY) can also reveal the presence of chemical exchange processes, for which the methods are also known as exchange spectroscopy (EXSY).For small molecules (M r < ca. 1000 Da) in non-viscous liquids at ambient temperatures, 1 H-1 H cross-peaks are negative (opposite sign to the diagonal-peaks) for the NOE and positive (same sign as the diagonal-peaks) for pairs of signals undergoing chemical exchange. For large molecules (M r > ca. 2000 Da), aggregates or with viscous solvents, the sign of the 1 H-1 H Overhauser effect undergoes a welldocumented inversion and cross-peaks become positive, appearing similar to those arising from chemical exchange processes.The theory of spin relaxation processes in general [3] and of NOEs in particular [2] is one of the most developed areas of magnetic resonance spectroscopy, meaning deviations from the behaviors described above are rare indeed. Herein, we report anomalous NOESY observations for a series of Csubstituted NH aziridines 1 a-d, for which the usual interpretations offered no acceptable explanation.During the development of methodology for the synthesis and desulfinylation of N-sulfinyl terminal aziridines by some of the current authors, [4] extensive spectroscopic analysis was carried out to establish the integrity of the aryl-substituted NH aziridines 1 a,b (due to prior literature mischaracterization [5] ).A NOESY spectrum of 2-phenylaziridine (1 a) in dry CD 2 Cl 2 at 298 K exhibited unexpected strong positive crosspeaks between the broad N-H resonance and all three CH protons of the aziridine (Figure 1 a), in addition to the anticipated NOEs producing negative cross-peaks between aziridine CH protons, characteristic of rapidly tumbling molecules. The aziridine CH protons also produced the expected negative cross-peaks with the nearby phenyl protons....

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Intramolecular proton nuclear Overhauser effect study of the solution conformation of valinomycin in dimethyl sulfoxide

Cited by 70 publications

References 33 publications

Protein folding

Protein folding

Membrane Conformations and Their Relation to Cytotoxicity of Asimicin and Its Analogues

Anomalous Nuclear Overhauser Effects in Carbon‐Substituted Aziridines: Scalar Cross‐Relaxation of the First Kind

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