The solution conformation of malformin A

Solution conformations of the cyclic pentapeptide plant-hormone malformin A, whose conformational freedom is constrained by an intramolecular disulfide bridge, are derived and presented here. The nmr and CD data of Ptak are used to place restrictions on the search for possible malformin A solution conformers of low energy. Only two distinct conformers were found to be consistent with Ptak's data. Both structures are characterized by an internally buried (solvent-shielded) D -Cys² amide proton, a seven-membered (1–3)hydrogen bond between (N–H) and (O?C), and a disulfide bridge conformation with a P chirality as manifested in the nmr study by the temperature independence of the amide proton chemical shifts for the D -Cys² and D -Leu⁴ residues and the negative sign of the long wavelength maximum in the CD spectrum, respectively. Inspection of space-filling molecular models of both structures indicates severe steric barriers to their rapid interconversion. Thus, it appears that only one of the two conformers may be present in solution. The difference in their calculated dipole moments (4.6 and 6.9D) suggests an experimental method for distinguishing between the two proposed solution structures.     

The conformation of adenovirus VAI-RNA in solution

The secondary structure of an adenovirus associated low molecular weight RNA (VAI-RNA) has been studied by partial digestion with T1-RNase and S1-endonuclease followed by T1-fingerprint analysis. The empirical secondary structure has been compared with two computer generated models based on minimal free energy of the structure. The results suggest that VAI-RNA in solution has a compact structure with a free energy of around -60 kcal with two stems and four bulge regions. The implication of this structure for the function of VAI-RNA is discussed.     

The conformation of echinomycin in DMSO solution

The conformation of the antibiotic echinomycin in DMSO solution has been determined from two-dimensional NMR and distance geometry calculation with distance constraints. Five converged conformations were calculated with NOE distance constraints followed by restraint energy minimization.     

The conformation of amylose in alkaline salt solution

The conformation of amylose in various solvents is discussed. It is shown that the changes in molecular volume of the polysaccharide (measured by viscosity) as potassium chloride is added to a solution of amylose at pH 12 are similar to those obtained on adding butan-1-ol to the solution. The viscosity number in both cases decreases to values less than that observed for amylose in water, in which Flory theta-conditions are approximated. The minimum value of the viscosity number, in fact, is identical to that observed on the addition of butan-1-ol and iodine to neutral aqueous solution of amylose—conditions known to result in a helical complex. It is concluded that amylose undergoes a coil-to-helix transition as potassium chloride is dadde to solutions of the polysaccharide at pH 12.     

The solution conformation of the Le chi group

The solution conformation of the non-reducing terminal Gal beta 1----4 (Fuc alpha 1----3)GlcNAc (Lewis X or Le chi) group in the oligosaccharide Lacto-N-fucopentaose (LNFP) III has been determined by high resolution 1H NMR spectroscopy and semi-empirical quantum mechanical calculations. The two methods give the same single conformer for the Le chi group showing close packing of the Gal and Fuc rings. The metal binding properties and homotypic oligomer formation of LNFP III have also been investigated by NMR spectroscopy. No evidence for metal binding or high-affinity homotypic oligomer formation has been found.     

The conformation of alpha-human atrial natriuretic polypeptide in solution

The three-dimensional structure of alpha-human ANP in solution was determined through the combined use of nuclear magnetic resonance spectroscopy and distance geometry. The results are based on distance constraints determined by nuclear Overhauser effect measurements and one disulfide bond. The structure is as follows. Three separate regions, which are Ser1-Cys7, Arg11-Ile15, and Gln18-Tyr28 each have some ordered structure. The remaining parts in the sequences of Gly9-Gly10 and Gly16-Ala17 act as hinges. And the C-terminal part is folded back toward the cyclic moiety. The conformation of alpha-hANP reported here is expected to give a better understanding of the relationships between its biological activities and three-dimensional structure.     

The folding and solution conformation of penicillin G acylase

The solution conformation properties of penicillin G acylase (EC 3.5.1.11) have been characterised by near- and far-ultraviolet circular dichroism, steady-state and time-resolved fluorescence spectroscopy and differential sedimentation velocity. The enzyme (86 kDa) was found to be spherical and stable unfolding over a narrow range of urea concentrations in an apparently cooperative fashion with a mid-point of 4.5 M urea. Separation of its constituent alpha and beta peptides (23.8 kDa and 62.2 kDa, respectively) was accompanied by loss of enzyme activity and unfolding, the kinetics of unfolding being highly dependent upon urea concentration. Urea gradient gel electrophoresis showed that the separated beta peptide aggregates over a wide range of urea concentrations but that the alpha peptide refolds reversibly to a compact state. Physical studies showed that the refolded alpha peptide has a compact but asymmetric structure with more alpha helix than the native enzyme, but is more sensitive to denaturant. The latter is suggested to be due to a hydrophobic patch detected by 8-anilino-1-naphthalene sulfonic acid binding and which is normally covered by the beta peptide in the native enzyme. The results of these investigations indicate that the alpha peptide constitutes a folding domain and suggest that it plays a key role in folding of the precursor for penicillin acylase.     

The solution conformation of C-glycosyl analogues of the sialyl-Tn antigen

The conformational behavior of two C-glycosyl analogues of the sialyl-Tn antigen has been determined by a combination of NMR methods and molecular mechanics calculations. Both compounds show a major solution conformation that is drastically different from the major one of the natural compound.     

Solid-state and solution conformation of scleroglucan

A potentiometric-titration procedure, in which samples are always exposed to an excess of I₂-KI has been developed for measuring iodine-binding capacity of starches. Binding capacity of amylose under these conditions is ～30% as opposed to 20% by conventional potentiometric titration. Spectrophotometric absorbance is essentially the same for either method, but is proportional to potentiometric values only in the excess-iodine titration procedure. Effects of variation of concentration of I₂, KI, and phosphate buffer and of temperature on the reaction have been examined. Calculations based on concentration of reactants in solution indicate that the binding species varies from I₃^? at 10^?1m KI to I₁₁^? at 5 × 10^?4m KI.     

The compact domain conformation of human Glu-plasminogen in solution.

A complete understanding of the accelerating mechanisms of plasminogen activation and fibrinolysis necessarily requires structural information on the conformational forms of plasminogen. Given the absence of high-resolution structural data on plasminogen the use of lower resolution approaches has been adopted. Two such approaches have previously indicated a compact conformation of Glu-plasminogen (Tranqui, L., Prandini, M., and Chapel, A. (1979) Biol. Cellulaire, 34, 39-42; Bányai, L. and Patthy, L. (1985) Biochim. Biophys. Acta, 832, 224-227) whereas a third has suggested a fairly extended conformation (Mangel, W., Lin, B. and Ramakrishnan, V. (1990) Science, 248, 69-73). Native Glu-plasminogen has been investigated using small-angle X-ray scattering (SAXS) experiments. It is concluded that this molecule in solution is compact (radius of gyration, RG 3.05 +/- 0.02 nm and maximum intramolecular distance, Im 9.1 +/- 0.3 nm) and that the data are consistent with the right-handed spiral structure observed using electron microscopy by Tranqui et al. (1979). A spiral structure of native plasminogen would have important implications for the conformational response of plasminogen to fibrin and concomitant stimulation of plasminogen activation.     

The solution conformation Ac-Pen-Arg-Gly-Asp-Cys-OH,a potent fibrinogen receptor antagonist

The solution conformation of , a potent fibrinogen receptor antagonist, was characterized in DMSO-d₆ by the combination of nmr and molecular modeling. The conformational space available to the peptide was explored using a distance geometry algorithm with distance constraints derived from ¹H-nmr spectra. The dynamics of the peptide were examined by relaxation time measurements and low temperature studies. The results from the low temperature studies suggest that the peptide backbone does not exist in a single, well-defined conformation but undergoes exchange between multiple conformers. This result is consistent with the inability to find a single structure that satisfies all the nmr-derived constraints. The constraints could only be satisfied by considering pairs of conformers to represent the experimental data. The low energy conformers comprise type II′ or type V β-turns with distinct side-chain directionality. The Arg-Gly-Asp portion of the ring is flexible and can be described by amide-plane rotations of the Arg-Gly and Gly-Asp peptide bonds. Although some backbone flexibility is evident, the incorporation of β,β-dimethyl cysteine imparted greater conformational rigidity as compared to the previously studied cyclic pentapeptide, . © 1993 John Wiley & Sons, Inc.     

Preferential conformation of substance P in solution

The three-dimensional structure of substance P has been studied by 1H-NMR, (500 MHz), and by circular dichroism (CD) in different solvents. The analysis of the different NMR parameters suggest that substance P adopts a rather extended structure in dimethylsulfoxide and pyridine. In water, besides the aggregation phenomenon, the monomeric substance P presents a complex conformational equilibrium. The addition of sodium dodecylsulfate to the aqueous solution induces, as shown by CD spectroscopy, a preferential alpha-helical conformation. And in methanol three structural conclusions may be drawn: the flexibility of the N-terminal Arg-Pro-Lys, the alpha-helical structure of Pro4-Gln5-Gln6-Phe7-Phe8 and the interaction of the C-terminal carboxamide with the primary amides from both glutamines.     

The mean conformation of N-acetylamino acid N'-methylamides in dimethyl sulfoxide solution

The mean conformation of a series of N-acetylamino acid N'-methylamides in dimethyl sulfoxide (DMSO) was determined by 1H-NMR and 13C-NMR methods.The series investigated consisted of derivatives of DL-Ala, DL-Asn, Gln, His, DL-Ile, DL-Leu, Met, DL-Pro, DL-Phe, Ser, Thr, Trp, Tyr, DL-Val, DL-Nva, and dl-Nle. It was found that the conformational equilibria in DMSO are dominated by C5 and C7eq forms.The amounts of these forms in the equibbria were found to be roughly proportional to the Boltzmann probabilities for the occurrence of a definite form, as calculated theoretically by Vasquez et al.(Macromolecules 16 (1983) 1043).Exceptions to this rule were DL-Pro and, to a lesser extent, Ser, Asn and Trp derivatives.     

The conformation of 1,6-anhydrolactose and its hexa-acetate in solution.

The conformation of 1,6-anhydrolactoase (1) has been investigated by n.m.r. spectroscopy and molecular mechanics calculations. For a solution in D2O, the 1,6-anhydroglucopyranoid ring has a 1C4 conformation, whereas there is a approximately 1:1 equilibrium between the 1C4 and the BO,3 conformations in (CD3)2SO. There is restricted flexibility with phi -80 +/- 20 degrees and psi -120 +/- 40 degrees. The hexa-acetate (2) of 1 shows a similar conformational behaviour.     

The conformation of the d(ACCCGGGT) duplex in aqueous solution

The nonexchangeable base and sugar protons of the octanucleotide d(ACCCGGGT)2 have been assigned using two dimensional homonuclear Hartmann-Hahn relayed spectroscopy (HOHAHA), double quantum filtered homonuclear correlation spectroscopy (DQFCOSY) and nuclear Overhauser spectroscopy (NOESY) in D2O at 12 degrees C. The observed NOE's between the base protons and their own H2' protons and between the base protons and the H2' protons of the 5' adjacent nucleotide and the observed coupling constants between the deoxyribose 1' and 2',2' protons indicate that this duplex assumes a right-handed B-type helix conformation in solution.