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At least 937 records · Page 52Linked to original sources
PubMed2002

A conformational analysis of Walker motif A [GXXXXGKT (S)] in nucleotide-binding and other proteins.

The sequence GXXXXGKT/S, popularly known as Walker motif A, is widely believed to be the site for binding nucleotides in many proteins. Examination of the crystal structures in the Protein Data Bank showed that about half of the examples having these sequences do not bind or use nucleotides. Data analyses showed 92 different Walker sequences of the variable quartet (XXXX). Ramachandran angles in this segment revealed conformational similarity in the group of 45 proteins, known to bind or utilize nucleotides. The conformations of this segment in other proteins differ widely and it is not known whether they play any role in their functions. A flip of a peptide unit at different locations, with little change in the backbone conformation was noted in nine pairs of these proteins having same Walker sequence. An examination of the immediate neighborhood of the Walker sequence indicates that this region is preceded by a beta-strand and followed by an alpha-helix, resulting in the motif beta-W-alpha, an invariant feature amongst nucleotide-binding proteins.

Amino Acid Motifs↗
PubMed1993

Solution conformational analysis of the alpha-zein proteins of maize.

Small angle x-ray scattering and viscometric analyses of the alpha-zeins of maize in solution indicated that the molecules were asymmetric. Structure predictions of consensus sequences for the two classes of alpha-zeins, Z19 and Z22, were in good agreement with the alpha-helical contents determined by circular dichroism. Dimensions determined by small angle x-ray scattering and viscometry indicated a predominantly alpha-helical conformation. The data are discussed in relation to models for the solution conformation and to earlier models for alpha-zeins structure.

Amino Acid Sequence↗
PubMed1990

Three-dimensional structure of the oligosaccharide terminus of globotriaosylceramide and isoglobotriaosylceramide in solution. A rotating-frame NOE study using hydroxyl groups as long-range sensors in conformational analysis by 1H-NMR spectroscopy.

Spatial structures of the oligosaccharide parts of globotriaosylceramide, Gal(alpha 1-4)Gal(beta 1-4)Glc(beta 1-1)Cer (Cer = ceramide) and isoglobotriaosylceramide, Gal(alpha 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer were investigated in (C2H3)2SO solution by means of laboratory and rotating frame NOE, hydroxyl protons being used as long-range sensors defining the distance constraints. Both oligosaccharides were found to exist in more than one conformation interconverting rapidly on the NMR time scale. The conformation of the Gal(alpha 1-4)Gal(beta 1-4)Glc beta trisaccharide dissolved in 2H2O appeared to be the same as that of the corresponding part of the glycosphingolipid in (C2H3)2SO solution.

Carbohydrate Conformation↗
PubMed1998

Conformation-function relationship of vitamin D: conformational analysis predicts potential side-chain structure.

In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group concept. In the present study, we used this active space group concept to analyze the conformation-activity relationship of about 40 representative potent 1alpha,25-dihydroxyvitamin D3 analogues. We initially listed structural modifications in the side chain of potent vitamin D analogues and estimated their potency factor. Possible side-chain conformations of representative analogues were calculated by the molecular mechanics method and plotted on a dot map compared with the regions A, G, EA, and EG. The cell-differentiating potency of the analogues was correlated with our active space group concept with few exceptions. Among potent analogues with a natural configuration at C(20), the side chains of those with a 22-oxa, 22-ene, 16-ene, or a 18-nor modification were located in front of region EA (termed F). The side chains of the most potent 20-epi-22-oxa-24-homovitamin D analogues were concentrated at the left side of the EA region (L-EA). Thus, the side chains of almost all potent analogues were distributed around the EA region, and potency increased in the order A, F, EA, and L-EA.

Calcitriol↗
PubMed2000

Conformational analysis in solution of C(2)-symmetric 1, 1'-binaphthyl derivatives by circular dichroism spectroscopy and cholesteric induction in nematic mesophases

The twisting ability of a series of 1,1'-binaphthalene compounds used as dopants in nematic solvents has been related to the dihedral angle theta between the two naphthalene moieties. While in the case of the more flexible compounds the sign and value of the helical twisting power is affected by several structural features that prevent a simple assignment of the conformation, in the presence of a covalent bridge that restricts the rotation around the C(1)-C(1') bond a reliable estimate of the conformational helicity could be obtained. This technique is complementary to CD spectroscopy that, for the investigated molecules, presents the same exciton patterns irrespective of the actual theta value.

Journal Article↗
PubMed1990

Conformational analysis of the tumor-associated carbohydrate antigen 19-9 and its Lea blood group antigen component as related to the specificity of monoclonal antibody CO19-9.

A structural comparison between the synthetic, tumor-associated 19-9 tetrasaccharide, NeuAc alpha 2----3Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 and its Lea blood group antigen component, Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 was carried out by two-dimensional 1H NMR spectroscopy and hard-sphere energy calculations. Significant chemical shift differences between the two molecules were detected only for protons at or near the linkage site of NeuAc to the Lea trisaccharide core. Coupling constants for the ring protons of both molecules did not suggest major deviation from the 4C1 chair conformation for Gal and GlcNAc, the 1C4 conformation for Fuc, or the 2C5 conformation for NeuAc. Two-dimensional nuclear Overhauser enhancement experiments revealed through-space, inter-proton interactions that corresponded to some extent with those predicted by diffraction data and hard-sphere energy minimization programs for both saccharides. However, a significant number of interactions did not obey the distance dependence predicted from a rigid structure model. These data suggest that, while the average conformation of the 19-9 antigen's Lea core may be invariant to NeuAc alpha 2----3Gal linkage, the dynamics of the Lea trisaccharide are altered upon sialylation. Data also indicate that the terminal NeuAc linkage is more flexible than the inter-residue bonds of the core trisacharide. This analysis, in combination with the fact that the monoclonal anti-19-9 antibody CO 19-9 does not cross-react with the Lea antigen, provides evidence in favor of NeuAc as an epitope-creating unit involved directly at the antibody binding site. However, given the possible role of variable dynamics in epitope formation, these results do not preclude crucial roles in antibody recognition for regions on the 19-9 antigen that are distanced from NeuAc.

Antibodies, Monoclonal↗
PubMed1997

Conformational analysis of Escherichia coli 30S ribosomes containing the single-base mutations G530U, U1498G, G1401C, and C1501G and the double-base mutation G1401C/C1501G.

Biochemical and genetic studies have pointed out the importance of several sites in 16S ribosomal RNA of Escherichia coli in the decoding process. These sites consist of the core of the decoding center (1400/1500 region) and two other segments (530 and 1050/1200 regions). To detect a possible structural link between these functionally related regions, we analyzed their sensitivity to conformational changes induced by mutations which are located in each of these regions and are known to affect the decoding process. The conformations of five segments of 16S rRNA (1-106, 406-569, 780-978, 997-1247, and 1334-1519) were analyzed by chemical probing of 30S ribosomes containing the following mutations: G530U, U1498G, G1401C, C1501G, and G1401C/C1501G. Ribosomes reconstituted with natural wild-type 16S RNA showed only minor conformational differences with respect to ribosomes isolated from cells. When 16S RNA made in vitro replaced natural 16S RNA, a slightly looser conformation of the central core region was found. Mutant ribosomes made by reconstitution with mutant 16S RNA made in vitro showed conformational effects which were in all cases localized to the region of secondary structure surrounding the site of mutation. Although the core of the decoding center (1400/1500 region) and the two other sites (530 and 1050/1200 regions) participating in the decoding function have been functionally linked, our data indicate that they are structurally independent. They also provide evidence for an unusual structure of the 1400/1500 decoding center, possibly involving noncanonical interactions. Furthermore, the absence of any conformational effect induced by the G530U mutation except at the site of mutation itself points to its direct, as opposed to indirect, involvement in the decoding function of the ribosome.

Base Sequence↗
PubMed1988

Conformational analysis of the dinucleotides 5'-methylphospho-N6-dimethyladenylyl-uridine (mpm62A-U) and 5'methylphospho-uridylyl-N6-dimethyladenosine (mpU-m62A) and of the trinucleotide U-m62A-U. A nuclear magnetic resonance and circular dichroic study.

NMR and CD studies were carried out on the dinucleotides 5'-methylphospho-N6-dimethyladenylyl-uridine (mpm62-U) and 5'-methylphospho-uridylyl-N6-dimethyladenosine (mpU-m62A) and on the trinucleotide U-m62A-U. A detailed comparison is given of the conformational features of mpm62A-U and mpU-m62A with the corresponding 5'-nonphosphorylated dinucleotides m62A-U and U-m62A, respectively. The behaviour of the trinucleotide U-m62A-U is compared with the properties of the constituent dinucleotides U-m62A and mpm62A-U. Chemical-shift and CD data were used to determine the amount of stacking interactions. For each compound NMR spectra were recorded at two or three sample concentrations in order to separate intermolecular and intramolecular base-base interactions. The coupling constants of the ribose ring are interpreted in terms of the N/S equilibrium, and population distributions along the backbone angles beta, gamma and epsilon are presented. The combined data indicate a strong similarity between mpm62A-U and m62A-U both in degree and in mode of stacking. In contrast, the existence of different types of stacking interactions in mpU-m62A and U-m62A is suggested in order to explain the NMR and CD data. It is concluded that dinucleoside bisphosphates serve better as a model for the behaviour of trinucleotides than dinucleoside monophosphates. The trinucleotide U-m62A-U adopts a regular single-stranded stacked RNA structure with preference for N-type ribose and gamma+ and beta t backbone torsion angles. The difference in behaviour between the U-m62A- part of U-m62A-U and the dimer U-m62A is seen as a typical example of conformational transmission.

Adenine Nucleotides↗
PubMed2004

Synthesis and conformational analysis of 1-[2,4-dideoxy-4-C-hydroxymethyl-alpha-l-lyxopyranosyl]thymine.

Previously different types of nucleosides with a six-membered carbohydrate moiety have been evaluated for their potential antiviral and antibiotic properties and as building blocks in nucleic acid synthesis. However, a pyranose nucleoside with a 1,4-substitution pattern like 1-[2,4-dideoxy-4-C-hydroxymethyl-alpha-l-lyxopyranosyl]thymine (4) has not been studied yet. Modeling suggested that this nucleoside would show the (4)C(1) conformation in contrast to anhydrohexitol nucleosides (1) whose most stable conformation is (1)C(4). The key to the synthesis of 4 involves the stereoselective introduction of the hydroxymethyl group onto the C-4 carbon of the pyranose sugar. Attempts to achieve this via hydroboration/oxidation of a C-4'-exocyclic vinylic intermediate selectively yielded the undesired alpha-directed hydroxymethyl group. Therefore, we envisaged another approach in which the C-4 substituent was introduced upon treatment of 2,3-O-isopropylidene-1-O-methyl-4-O-phenoxythiocarbonyl-alpha-l-lyxopyranose with beta-tributylstannyl styrene. This allowed stereoselective beta-directed introduction of a 2-phenylethenyl group at C-4, which was converted via oxidation/reduction (OsO(4), NaIO(4)/NaBH(4)) into the desired 4-hydroxymethyl group (20). The resulting 1-O-methyl-2,3,6-tri-O-acetyl-protected sugar was coupled with silylated thymine, using SnCl(2) as Lewis acid (22). After suitable protection, Barton deoxygenation of the 2'-hydroxyl function of the obtained ribo-nucleoside yielded the desired 2'-deoxynucleoside 4, indeed showing the expected equatorial orientation of the thymine ring ((4)C(1)).

Carbohydrate Conformation↗
PubMed2006

Conformational analysis of an alpha3beta1 integrin-binding peptide from thrombospondin-1: implications for antiangiogenic drug design.

The integrin alpha3beta1 plays important roles in development, angiogenesis, and the pathogenesis of cancer, suggesting potential therapeutic uses for antagonists of this receptor. Recently, an alpha3beta1 integrin-binding site was mapped to residues 190-201 (FQGVLQNVRFVF) of the N-terminal domain of the secreted protein thrombospondin-1 (TSP1). This sequence displays diverse biological activities in vitro and inhibits angiogenesis in vivo. Herein we describe the NMR solution conformation of this segment in both water and dodecylphosphocholine micelles. While essentially unstructured in water, a more well-defined conformation is populated in micelles, particularly in the C-terminal half of the peptide and correlated with increased biological activity of the micellar peptide. The data suggested that the residues that are critical for biological activity are contained in a structurally well-defined segment of the peptide. These data support the role of the NVR motif as a required element of full-length TSP1 for specific molecular recognition by the alpha3beta1 integrin.

Angiogenesis Inhibitors↗
PubMed1996

Conformational analysis of acetylcholine and related choline esters.

The crystal structures of carbamoylcholine [2-(carbamoyloxy)-N,N,N-trimethylethanaminium] chloride, bromide and iodide, methoxycarbonylcholine [2-(methoxycarbonyloxy)-N,N,N-trimethylethanaminium] iodide, acetylcholine [2-(acetyloxy)-N,N,N-trimethylethanaminium] chloride and succinylcholine ¿2,2'-[(1,4-dioxo-1,4-butanediyl)bis(oxy)]bis(N,N,N-trimethylet hanaminium)¿ iodide have been redetermined at 105 K in order to obtain detailed and accurate information on the geometry of choline esters and to elucidate the conformationally dependent changes of geometry. The conformational flexibility and the preferred conformations are elucidated based on results obtained from X-ray crystallographic studies and molecular mechanics (MM2) calculations. The usefulness of molecular mechanics calculations for quaternary ammonium ions is discussed.

Acetylcholine↗
PubMed2001

Synthesis and solution conformational analysis of 2,3-anhydro-3-C-[(1R)-2,6-anhydro-1-deoxy-1-fluoro-D-glycero-D-gulo-heptitol-1-C-yl]-beta-D-gulo-furanose: first example of a monofluoromethylene-linked C-disaccharide.

Condensation of 2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosylcarbaldehyde with isolevoglucosenone induced by Et(2)AlI, followed by epoxidation, gave an aldol that was fluorinated into a monofluoromethylene C-glucopyranoside that was converted into the title C-disaccharide 1. Its conformational behavior in water has been studied by using a combination of NMR spectroscopy (J and NOE data) and molecular mechanics calculations.

Carbohydrate Conformation↗
PubMed1996

Conformational analysis of pentapeptide sequences matching a proposed recognition motif for lysosomal degradation.

A selective pathway for the degradation of specific long-lived cytosolic proteins is activated in response to starvation in vivo or to serum withdrawal from cultured cells. It involves recognition of a targeting motif by a member of the hsp70 family. A 5-residue targeting motif has been proposed on the basis of sequence comparisons. We investigate whether there is any structural basis for this motif being the true recognition signal. We examine the conformations of four motif peptides in proteins that are either known to be serum regulated or are from related vertebrate species, and two equivalent peptides in bacterial proteins that closely resemble other regulated proteins. Our studies show that all the motif sequences are located near the ends of surface helices with one or more of the residues buried in the structure, yet it is known that members of the hsp70 family tend to interact with extended peptide chains. Furthermore, recognition by these proteins generally requires a specific ordering of key residues, yet the motif implies a largely order-independent sequence characterized by residue type only. We conclude that the proposed motif is unlikely to be the true targeting signal for lysosomal degradation unless additional factors apply.

Amino Acid Sequence↗
PubMed1995

X-ray crystal structure and conformational analysis of N-(3-dimethylaminopropyl)-N-(ethylaminocarbonyl)-6-(2-propenyl)er goline -8 beta-carboxamide (Cabergoline): comparison with bromocriptine and lisuride and a hypothesis for its high dopaminergic activity.

The crystal structure of Cabergoline, a potent and long lasting prolactin lowering agent interacting with the D2 dopamine receptors, has been determined by X-ray diffraction data. The structural data represent the starting point for a computational study, where the molecular mechanisms approach was used to explore the motion of all unconstrained torsion angles. Two different conformations related to energetic minima have been found, one of them in agreement with the experimental crystal structure. Both conformations are shape compared with Bromocriptine and Lisuride, two dopaminergic ergoline derivatives with C-8 beta and C-8 alpha substituents of the ergoline ring, respectively. We observe that the C-8 beta Cabergoline assumes the overall three-dimensional features of C-8-alpha-ergolines in one of its low-energy conformations.

Bromocriptine↗
PubMed2005

Conformational analysis of 2,2'-bithiophene: a (1)H liquid crystal NMR study using the (13)C satellite spectra.

We have obtained a very large data set of spectral parameters from the analysis of (1)H NMR and (13)C satellite spectra of 2,2'-bithiophene dissolved in anisotropic, partially orienting mesophases. In particular, this parameter set includes 33 dipolar couplings, which are directly related to the interatomic distances, the dihedral angle phi between the two thiophenic rings, and the anisotropic solute-solvent interaction potential. This allows an exhaustive investigation of the conformational equilibrium of 2,2'-bithiophene in a liquidlike phase. Comparison with the predictions of high-level theoretical calculations for the isolated molecule provides evidence of a strong flattening as well as the sharpening effect of the medium on the conformer population. The approximations needed to apply vibrational corrections to flexible molecules are discussed in detail and some general conclusions concerning their effect on structure and conformational equilibria are proposed.

Carbon Isotopes↗
PubMed2002

Absolute configuration and conformational analysis of a degradation product of inhalation anesthetic Sevoflurane: A vibrational circular dichroism study.

1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane, compound B, is a product obtained in the degradation of the anesthetic Sevoflurane. Enantiopure (+)-B was investigated using vibrational circular dichroism (VCD). Experimental absorption and VCD spectra of (+)-B in CDCl(3) solution in the 2,000-900 cm(-1) region are compared with the ab initio predictions of absorption and VCD spectra obtained from density functional theory using B3LYP/6-31G* basis set for different conformers of (S)-1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane. This comparison indicates that (+)-B is of the (S)-configuration in CDCl(3) solution, in agreement with previous literature results. Our results also indicate that this compound adopts six predominant conformations in CDCl(3) solution.

Anesthetics, Inhalation↗
PubMed2001

Cyclic homooligomers from sugar amino acids: synthesis, conformational analysis, and significance.

Sugar amino acids (SAAs) were designed as new building blocks carrying an amino group and a carboxyl group on a carbohydrate scaffold. By exploiting standard solid- and solution-phase coupling procedures, linear and cyclic homooligomers containing glucosyluronic acid methylamine (Gum) were synthesized. We achieved a high yield and a very short coupling time for the oligomerization and cyclization of sequences encompassing two, three, four, and six Gum units. The synthesis of cyclic oligomers containing only SAAs as repetitive units has not been reported before. The conformational preferences in aqueous solution of the cyclic derivatives and their applications as potential host molecules are described herein. Benzoic acid and p-nitrophenol were chosen as model guest molecules to study the formation of cyclodextrin-like inclusion complexes. The complexation behavior of the cyclic hexamer was proved from three different points of view: chemical shifts, longitudinal relaxations (T(1)), and diffusion coefficients. All of them showed different values for host and guest molecules measured independently and in the presence of each other.

Amino Acids↗