Folded Conformation (folded + conformation)

Distribution by Scientific Domains
Distribution within Chemistry


Selected Abstracts


Binding of the volatile general anesthetics halothane and isoflurane to a mammalian ,-barrel protein

FEBS JOURNAL, Issue 2 2005
Jonas S. Johansson
A molecular understanding of volatile anesthetic mechanisms of action will require structural descriptions of anesthetic,protein complexes. Porcine odorant binding protein is a 157 residue member of the lipocalin family that features a large ,-barrel internal cavity (515 ± 30 Å3) lined predominantly by aromatic and aliphatic residues. Halothane binding to the ,-barrel cavity was determined using fluorescence quenching of Trp16, and a competitive binding assay with 1-aminoanthracene. In addition, the binding of halothane and isoflurane were characterized thermodynamically using isothermal titration calorimetry. Hydrogen exchange was used to evaluate the effects of bound halothane and isoflurane on global protein dynamics. Halothane bound to the cavity in the ,-barrel of porcine odorant binding protein with dissociation constants of 0.46 ± 0.10 mm and 0.43 ± 0.12 mm determined using fluorescence quenching and competitive binding with 1-aminoanthracene, respectively. Isothermal titration calorimetry revealed that halothane and isoflurane bound with Kd values of 80 ± 10 µm and 100 ± 10 µm, respectively. Halothane and isoflurane binding resulted in an overall stabilization of the folded conformation of the protein by ,0.9 ± 0.1 kcal·mol,1. In addition to indicating specific binding to the native protein conformation, such stabilization may represent a fundamental mechanism whereby anesthetics reversibly alter protein function. Because porcine odorant binding protein has been successfully analyzed by X-ray diffraction to 2.25 Å resolution [1], this represents an attractive system for atomic-level structural studies in the presence of bound anesthetic. Such studies will provide much needed insight into how volatile anesthetics interact with biological macromolecules. [source]


On the molecular basis of the recognition of angiotensin II (AII)

FEBS JOURNAL, Issue 5 2003
NMR structure of AII in solution compared with the X-ray structure of AII bound to the mAb Fab13
The high-resolution 3D structure of the octapeptide hormone angiotensin II (AII) in aqueous solution has been obtained by simulated annealing calculations, using high-resolution NMR-derived restraints. After final refinement in explicit water, a family of 13 structures was obtained with a backbone RMSD of 0.73 ± 0.23 Å. AII adopts a fairly compact folded structure, with its C-terminus and N-terminus approaching to within ,,7.2 Å of each other. The side chains of Arg2, Tyr4, Ile5 and His6 are oriented on one side of a plane defined by the peptide backbone, and the Val3 and Pro7 are pointing in opposite directions. The stabilization of the folded conformation can be explained by the stacking of the Val3 side chain with the Pro7 ring and by a hydrophobic cluster formed by the Tyr4, Ile5 and His6 side chains. Comparison between the NMR-derived structure of AII in aqueous solution and the refined crystal structure of the complex of AII with a high-affinity mAb (Fab131) [Garcia, K.C., Ronco, P.M., Verroust, P.J., Brunger, A.T., Amzel, L.M. (1992) Science257, 502,507] provides important quantitative information on two common structural features: (a) a U-shaped structure of the Tyr4-Ile5-His6-Pro7 sequence, which is the most immunogenic epitope of the peptide, with the Asp1 side chain oriented towards the interior of the turn approaching the C-terminus; (b) an Asx-turn-like motif with the side chain aspartate carboxyl group hydrogen-bonded to the main chain NH group of Arg2. It can be concluded that small rearrangements of the epitope 4,7 in the solution structure of AII are required by a mean value of 0.76 ± 0.03 Å for structure alignment and ,,1.27 ± 0.02 Å for sequence alignment with the X-ray structure of AII bound to the mAb Fab131. These data are interpreted in terms of a biological ,nucleus' conformation of the hormone in solution, which requires a limited number of structural rearrangements for receptor,antigen recognition and binding. [source]


Peptide dynamic fingerprints: a tool for investigating the role of conformational flexibility for GLP-1 analogs affinity

JOURNAL OF PEPTIDE SCIENCE, Issue 8 2005
Dr M. Adenot
Abstract Glucagon-like peptide-1 (GLP-1) is a 30-residue peptide implicated in short-term appetite regulation. Its analogs are presumed to be potential drugs against obesity and non-insulin dependent diabetes mellitus (NIDDM or type 2 diabetes). This study examined how the dynamic fingerprints can be used for establishing dynamics,activity relationships in a series of peptides for which the mechanism of action is unknown and in which mutations can cause an increase or decrease in biological activity. The 3D autocorrelation method was used to generate maps of both active and inactive analogs. As the active conformation of GLP-1 is not yet clearly defined, the dynamic fingerprints of peptides in an aqueous environment were compared to explain the high affinity of the peptide for its receptor. The suggestion that the peptide could bind to the receptor in a folded conformation has been examined. In the case of the GLP-1 analogs, it was shown that the folding tendency cannot be directly related to affinity values and the results do not favor a folded active conformation model of GLP-1. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source]


Titanium-Catalyzed Norbornene Oligomerization.

MACROMOLECULAR RAPID COMMUNICATIONS, Issue 22 2006
3- exo -Disyndiotactic Structure, Isolation of a Crystalline Heptamer with a
Abstract Summary: Norbornene (NB) was oligomerized at 0,°C using AlEt2Cl-TiCl4 at a monomer/titanium molar ratio of about 11. The oligomerization product consists of a fraction soluble in diethyl ether, amorphous by X-ray examination, and of a crystalline fraction, insoluble in diethyl ether. The crystalline fraction was shown by powder X-ray diffraction to consist of a NB heptamer. Single-crystal X-ray analysis indicated that the heptamer had a stereoregular 2,3- exo -disyndiotactic structure. The heptamer adopts a strained, highly irregular, folded conformation in the crystalline state. Structural differences with respect to NB oligomers obtained with zirconocene catalysts are discussed. A view of the molecular structure of the crystalline NB heptamer. [source]


2-(1,3-Dithian-2-yl)benzaldehyde and N -{2-[2-(1,3-dioxan-2-yl)phenoxy]­ethyl}phthalimide

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 6 2000
Paul G. Jene
The crystal structures of two elaborated-porphyrin precursors have been determined. In the crystalline state, 2-(1,3-di­thian-2-yl)­benz­aldehyde, C11H12OS2, has its di­thiane ring in a slightly distorted chair conformation. The mol­ecules pack in anti-parallel chains. N -{2-[2-(1,3-Dioxan-2-yl)­phenoxy]­ethyl}­phthal­imide, C20H19NO5, is in a folded conformation. The dihedral angle between the phthal­imide and phenyl planes is 80.07,(3)°. In the crystalline states, mol­ecules stack on top of one another. [source]


Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2006
Eric Marr
Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5,Å resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity. [source]


Synthesis and X-ray study of the 6-(N -pyrrolyl)purine and thymine derivatives of 1-aminocyclopropane-1-carboxylic acid

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2004
M. Cetina
Abstract:, The novel purine and pyrimidine derivatives of 1-aminocyclopropane-1-carboxylic acid 1 and 2 were obtained by alkylation of 6-(N -pyrrolyl)purine and thymine with methyl 1-benzamido-2-chloromethylcyclopropanecarboxylate. X-ray crystal structure analysis shows that the cyclopropane rings in 1 and 2 posses Z -configuration. The cyclopropane ring atoms and attached atoms of the benzamido and methoxycarbonyl moiety of both molecules are disposed perpendicularly to each other. The carbonyl oxygen of the methoxycarbonyl moiety adopts in both compounds a synperiplanar conformation with respect to the midpoint of the distal bond of the cyclopropane ring. The torsion angles , and , for the 1-aminocyclopropane-1-carboxylic acid residue in 1 and 2 correspond to a folded conformation, while the torsion angles , define antiperiplanar conformation. Intermolecular hydrogen bonds connect the molecules of 1 into dimers. Each dimer is hydrogen-bonded with four ethanol molecules, thus forming discrete unit. On the contrary, intermolecular hydrogen bonds link the molecules of 2 generating three-dimensional network. [source]


Polymorphism Versus Thermochromism: Interrelation of Color and Conformation in Overcrowded Bistricyclic Aromatic Enes

CHEMISTRY - A EUROPEAN JOURNAL, Issue 12 2006
P. Ulrich Biedermann Dr.
Abstract The nature of the thermochromic form of overcrowded bistricyclic aromatic enes (BAEs) has been controversial for a century. We report the single-crystal X-ray structure analysis of the deep-purple and yellow polymorphs of 9-(2,7-dimethyl-9H -fluoren-9-ylidene)-9H -xanthene (11), which revealed the molecules in a twisted and a folded conformation, respectively. Therefore, the deeply colored thermochromic form B of BAEs is identified as having a twisted conformation and the ambient-temperature form A as having a folded conformation. This relationship between the color and the conformation is further supported by the X-ray structures of the deep-purple crystals of the twisted 9-(9H -fluoren-9-ylidene)-9H -xanthene (10), and of the yellow crystals of the folded 9-(11H -benzo[b]fluoren-11-ylidene)-9H -xanthene (12). Based on this conclusive crystallographic evidence, eleven previously proposed rationales of thermochromism in BAEs are refuted. In the twisted structures, the tricyclic moieties are nearly planar and the central double bond is elongated to 1.40 Å and twisted by 42°. In the folded structures, the xanthylidene moieties are folded by 45° and the fluorenylidene moieties by 18,20°. Factors stabilizing the twisted and folded conformations are discussed, including twisting of formal single or double bonds, intramolecular overcrowding, and the significance of a dipolar aromatic "xanthenylium-fluorenide" push,pull structure. [source]


Conformationally Biased Selective Alkylation of trans -Cyclohexane-1,2-bis(sulfonamide) Assisted by Solvent-Tuned Protecting Groups: Applications to the Synthesis of a Large Optically Active Polyazamacrocycle,

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2006
Carmen Peña
Abstract The selective alkylation of (R,R)-cyclohexane-1,2-bis(sulfonamide) with trityl bromoalkyl ethers has been studied in detail. The major formation of either mono- or dialkylated compounds clearly depends on the right combination of protecting groups and the reaction solvent. An exhaustive study suggests that this effect can be reasonably explained by the conformational preferences of the monoalkylated compounds, which also depend on the reaction medium, solvophobic effects and weak intramolecular interactions. Structural analysis by NOE measurements showed the presence of folded conformations in solution for all the tested examples. Monte Carlo conformational searches supported this proposal, showing a very good correlation between the fraction of folded species and the selectivity towards monoalkylation. Finally, tuning of the reaction conditions, leading to either extended or folded conformations of the monoalkylated synthetic intermediates, was exploited for the efficient synthesis of a large optically active polyazamacrocycle. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source]


Peptide T revisited: conformational mimicry of epitopes of anti-HIV proteins

JOURNAL OF PEPTIDE SCIENCE, Issue 4 2001
Delia Picone
Abstract Peptide T (ASTTTNYT), a fragment corresponding to residues 185,192 of gp120, the coat protein of HIV, is endowed with several biological properties in vitro, notably inhibition of the binding of both isolated gp120 and HIV-1 to the CD4 receptor, and chemotactic activity. Based on previous nuclear magnetic resonance (NMR) studies performed in our laboratory, which were consistent with a regular conformation of the C -terminal pentapeptide, and SAR studies showing that the C -terminal pentapeptide retains most of the biological properties, we designed eight hexapeptides containing in the central part either the TNYT or the TTNY sequence, and charged residues (D/E/R) at the two ends. Conformational analysis based on NMR and torsion angle dynamics showed that all peptides assume folded conformations, albeit with different geometries and stabilities. In particular, peptides carrying an acidic residue at the N -terminus and a basic residue at the C -terminus are characterized by stable helical structures and retain full chemotactic activity. The solution conformation of peptide ETNYTR displays strong structural similarity to the region 19,26 of both bovine pancreatic and bovine seminal ribonuclease, which are endowed with anti-HIV activity. Moreover, the frequent occurrence, in many viral proteins, of TNYT and TTNY, the two core sequences employed in the design of the hexapeptides studied in the present work, hints that the sequence of the C -terminal pentapeptide TTNYT is probably representative of a widespread viral recognition motif. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source]


New permanently charged phenanthridinium,nucleobase conjugates.

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 12 2003
Interactions with nucleotides, polynucleotides, recognition of ds-polyAH+
Abstract N -Methyl-8-aminophenathridinium,uracil and ,adenine conjugates possessing a nucleobase attached at the phenanthridinium 8-amino group by a trimethylene spacer were prepared in the form of water-soluble hydrogensulfate salts. Spectroscopic characteristics of the conjugates reveal the formation of folded conformations in water characterized by intramolecular aromatic stacking between the phenanthridinium unit and the tethered nucleobase. The conjugates form 1:1 complexes in water with either complementary or non-complementary nucleotides, giving log Ks values between 1 and 2 and showing a lack of any base recognition. Also, the binding studies with single-stranded polynucleotides showed no preference of conjugates to polynucleotides containing complementary nucleobases. At pH 5, the N -methylphenanthridinium,adenine conjugate exhibited preferred binding to double-stranded (ds-) polyAH+, whereas its protonated analogue bound preferably to polyU. The results reveal that the presence of protonated or permanently charged intercalator units in the conjugates dramatically changes their binding preferences for polynucleotides. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Characterization of folded conformations in a tetrapeptide containing two tryptophan residues by vibrational circular dichroism,

CHIRALITY, Issue 1E 2009
Ana G. Petrovic
Abstract The intramolecularly hydrogen bonded conformations of the tetrapeptide Boc-Trp-Aib-Gly-Trp-OMe (WUGW) are investigated using experimental and quantum chemical predictions of vibrational circular dichroism (VCD) in the 1800,1550 cm,1 region. The predicted VCD spectrum, for a conformation (conformer A) obtained from optimization of crystal structure, reproduced the dominant negative VCD band observed experimentally in CH3OH and CHCl3 solvents. However, the predicted VCD spectrum of Conformation A also has an extra positive band which is not seen in the experimental spectra. This mismatch appears to be due to the lack of solvent influence in the quantum chemical geometry optimizations. However, Conformations I and II, obtained, respectively, from constrained optimization of crystal and NMR structures, mimic the solvent stabilized structures and are predicted to have dominant negative VCD band as found in the experimental spectra. It is noted that, for the peptide investigated here, unconstrained quantum chemical geometry optimizations in vacuum converged to structures that are not the realistic models of conformations found in solution. It is also noted that undertaking quantum chemical vibrational property calculations directly using geometries obtained from crystal data or NMR data resulted in unrealistic vibrational frequencies and descriptions. However, constraining the backbone dihedral angles to those found in condensed medium, and optimizing the remaining geometrical parameters resulted in a better reproduction of the observed VCD in condensed medium. The vibrational origins of bands in all of the predicted VCD spectra for the WUGW-tetrapeptide have also been presented. Chirality 21:E76,E85, 2009. © 2009 Wiley-Liss, Inc. [source]