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1.
Comput Struct Biotechnol J ; 19: 2891-2904, 2021.
Article in English | MEDLINE | ID: mdl-34094000

ABSTRACT

The neurotrophins, i.e., Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin 3 (NT3) and Neurotrophin 4 (NT4), are known to play a range of crucial functions in the developing and adult peripheral and central nervous systems. Initially synthesized as precursors, i.e., proneurotrophins (proNTs), that are cleaved to release C-terminal mature forms, they act through two types of receptors, the specific Trk receptors (Tropomyosin-related kinases) and the pan-neurotrophin receptor p75NTR, to initiate survival and differentiative responses. Recently, all the proNTs but proNT4 have been demonstrated to be not just inactive precursors, but signaling ligands that mediate opposing actions in fundamental aspects of the nervous system with respect to the mature counterparts through dual-receptor complexes formation with a member of the VPS10 family and p75NTR. Despite the functional relevance, the molecular determinants underpinning the interactions between the pro-domains and their receptors are still elusive probably due to their intrinsically disordered nature. Here we present an evolutionary approach coupled to an experimental study aiming to uncover the structural and dynamical basis of the biological function displayed by proNGF, proBDNF and proNT3 but missing in proNT4. A bioinformatic analysis allowed to elucidate the functional adaptability of the proNTs family in vertebrates, identifying conserved key structural features. The combined biochemical and SAXS experiments shed lights on the structure and dynamic behavior of the human proNTs in solution, giving insights on the evolutionary conserved structural motifs, essential for the multifaceted roles of proNTs in physiological as well as in pathological contexts.

2.
Malays Orthop J ; 7(1): 74-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-25722812

ABSTRACT

UNLABELLED: Dislocation of the head of the radius may be either congenital, an isolated injury or more commonly part of a complex injury to the elbow such as the Monteggia fracturedislocation. Isolated traumatic radial head dislocation without associated injuries in children is a rare and easily missed condition. We report such a case in a 7-year-old boy without any associated injuries or co-morbid conditions. Initially the diagnosis was missed, and 6 weeks later open reduction was performed with annular ligament reconstruction surgery. At the one-year follow up, the patient had returned to most normal activities, showing only slight terminal restriction of pronation. We discuss the injury mechanism and management for the Monteggia fracturedislocation and review the available literature. KEY WORDS: radial head dislocation, traumatic, Monteggia fracturedislocation.

3.
Biochem Soc Trans ; 34(Pt 4): 605-6, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16856872

ABSTRACT

The unprocessed pro-form of the NGF (nerve growth factor), proNGF (NGF precursor, without signal peptide), has been suggested to have additional functions distinct from its role as a promoter of protein folding, i.e. apoptosis and/or neurotrophic activity. Aiming to gain insights into the specific molecular interactions that mediate proNGF biological activity and into the structural determinants stabilizing its pro-region, rm-proNGF (recombinant mouse proNGF) was expressed in Escherichia coli, refolded in vitro and characterized by physicochemical methods. X-ray solution scattering measurements (small angle X-ray scattering) revealed that rm-proNGF is dimeric in solution and appears to be anisometric when compared with the compact structure of the NGF dimer. Two structural models, a globular crab-like shape and an elongated rod-like shape, equally fit to the experimental results, pointing to an intrinsically structural disordered pro-region of NGF. The models obtained allowed the interpretation of TrkA (tropomyosin receptor kinase A) binding and activation assays in cell cultures, shedding new light on the key role of proNGF in neuronal survival and neurodegeneration.


Subject(s)
Nerve Growth Factor/chemistry , Nerve Growth Factor/metabolism , Protein Precursors/chemistry , Protein Precursors/metabolism , Animals , Computational Biology , Mice , Models, Molecular , Protein Folding , Protein Structure, Tertiary
4.
Carbohydr Res ; 340(3): 455-8, 2005 Feb 28.
Article in English | MEDLINE | ID: mdl-15680601

ABSTRACT

D-Hamamelose, a branched-chain ribose (2-C-(hydroxymethyl)-D-ribose), has been synthesized and its solid-state structure analyzed by (13)C CP MAS NMR spectra and X-ray data. The presence of the complex pattern of resonances in the anomeric region, as well as in the ring carbon region, in (13)C CP MAS NMR spectrum indicated that the mixture of four cyclic forms, alpha- and beta-furanoses, as well as both alpha- and beta-pyranoses were present in the solid-state. X-ray analysis of crystals showed that D-hamamelose belongs to the monoclinic system with unit cell: a=4.790A, b=8.671A, c=8.880A and beta=98.89 degrees , space group P2(1). The furanose ring has the (2)E conformation.


Subject(s)
Hexoses/chemistry , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Molecular Structure
5.
EMBO J ; 20(23): 6570-82, 2001 Dec 03.
Article in English | MEDLINE | ID: mdl-11726493

ABSTRACT

Dipeptidyl peptidase I (DPPI) or cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells vital for defense of an organism. The structure presented shows how an additional domain transforms the framework of a papain-like endopeptidase into a robust oligomeric protease-processing enzyme. The tetrahedral arrangement of the active sites exposed to solvent allows approach of proteins in their native state; the massive body of the exclusion domain fastened within the tetrahedral framework excludes approach of a polypeptide chain apart from its termini; and the carboxylic group of Asp1 positions the N-terminal amino group of the substrate. Based on a structural comparison and interactions within the active site cleft, it is suggested that the exclusion domain originates from a metallo-protease inhibitor. The location of missense mutations, characterized in people suffering from Haim-Munk and Papillon-Lefevre syndromes, suggests how they disrupt the fold and function of the enzyme.


Subject(s)
Cathepsin C/chemistry , Cathepsin C/genetics , Endopeptidases/chemistry , Serine Endopeptidases/chemistry , Amino Acid Sequence , Animals , Baculoviridae/metabolism , Binding Sites , Cell Line , Dimerization , Humans , Insecta , Models, Molecular , Molecular Sequence Data , Mutation, Missense , Papillon-Lefevre Disease/genetics , Papillon-Lefevre Disease/metabolism , Protein Conformation , Protein Folding , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Sequence Homology, Amino Acid , Substrate Specificity , Syndrome
6.
Acta Crystallogr D Biol Crystallogr ; 57(Pt 12): 1906-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11717513

ABSTRACT

The gene encoding for acetylxylan esterase from Bacillus pumilus has been cloned and expressed in Escherichia coli. The recombinant protein has been purified to homogeneity and crystallized. The crystals obtained are of regular shape of dimensions 0.05 x 0.05 x 0.05 mm with R32 symmetry and diffract to 2.0 A using synchrotron radiation.


Subject(s)
Acetylesterase/chemistry , Bacillus/enzymology , Acetylesterase/genetics , Crystallization , Crystallography, X-Ray , Protein Conformation , Recombinant Proteins/chemistry
7.
Acta Crystallogr D Biol Crystallogr ; 57(Pt 9): 1307-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11526327

ABSTRACT

The monoclonal antibody MNAC13 is a potent antagonist that prevents the binding of nerve-growth factor (NGF) to its tyrosine kinase A receptor (TrkA) in a variety of systems. Structural studies of the FabMNAC13 fragment were performed to gain insights into the mechanism of action of this potentially therapeutic monoclonal antibody. The optimal conditions for crystallization of FabMNAC13 were determined. Crystals appeared as prismatic bundles, displayed P2(1)2(1)2(1) space-group symmetry and diffracted to a resolution of 1.8 A. The unit-cell parameters were determined to be a = 52.73, b = 67.55, c = 111.43 A. The data set was 99.5% complete. Molecular replacement was performed, resulting in a correlation coefficient of 0.55 and an R value of 0.40. The structure refinement is now in progress.


Subject(s)
Antibodies, Monoclonal/chemistry , Immunoglobulin Fab Fragments/chemistry , Receptor, trkA/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Monoclonal/pharmacology , Crystallization , Crystallography, X-Ray , Immunoglobulin Fab Fragments/isolation & purification , Nerve Growth Factor/antagonists & inhibitors , Protein Conformation
8.
J Mol Graph Model ; 19(3-4): 288-96, 374-8, 2001.
Article in English | MEDLINE | ID: mdl-11449566

ABSTRACT

The alkaloid (-)-galanthamine is known to produce significant improvement of cognitive performances in patients with the Alzheimer's disease. Its mechanism of action involves competitive and reversible inhibition of acetylcholinesterase (AChE). Herein, we correctly predict the orientation and conformation of the galanthamine molecule in the active site of AChE from Torpedo californica (TcAChE) using a combination of rigid docking and flexible geometry optimization with a molecular mechanics force field. The quality of the predicted model is remarkable, as indicated by the value of the RMS deviation of approximately 0.5A when compared with the crystal structure of the TcAChE-galanthamine complex. A molecular model of the complex between TcAChE and a galanthamine derivative, SPH1107, with a long chain substituent on the nitrogen has been generated as well. The side chain of this ligand is predicted to extend along the enzyme active site gorge from the anionic subsite, at the bottom, to the peripheral anionic site, at the top. The docking procedure described in this paper can be applied to produce models of ligand-receptor complexes for AChE and other macromolecular targets of drug design.


Subject(s)
Acetylcholinesterase/chemistry , Cholinesterase Inhibitors/chemistry , Computer Simulation , Galantamine/chemistry , Models, Molecular , Alzheimer Disease/drug therapy , Animals , Catalytic Domain , Cholinesterase Inhibitors/therapeutic use , Crystallography, X-Ray , Galantamine/therapeutic use , Humans , Molecular Conformation , Nootropic Agents/chemistry , Nootropic Agents/therapeutic use , Protein Conformation , Software , Torpedo
9.
Proteins ; 42(2): 182-91, 2001 Feb 01.
Article in English | MEDLINE | ID: mdl-11119642

ABSTRACT

The 3D structure of a complex of the anti-Alzheimer drug galanthamine with Torpedo californica acetylcholinesterase is reported. Galanthamine, a tertiary alkaloid extracted from several species of Amarylidacae, is so far the only drug that shows a dual activity, being both an acetylcholinesterase inhibitor and an allosteric potentiator of the nicotinic response induced by acetylcholine and competitive agonists. The X-ray structure, at 2.5A resolution, shows an unexpected orientation of the ligand within the active site, as well as unusual protein-ligand interactions. The inhibitor binds at the base of the active site gorge, interacting with both the acyl-binding pocket and the principal quaternary ammonium-binding site. However, the tertiary amine group of galanthamine does not directly interact with Trp84. A docking study using the program AUTODOCK correctly predicts the orientation of galanthamine in the active site. The docked lowest-energy structure has a root mean square deviation of 0.5A with respect to the corresponding crystal structure of the complex. The observed binding mode explains the affinities of a series of structural analogs of galanthamine and provides a rational basis for structure-based drug design of synthetic derivatives with improved pharmacological properties. Proteins 2001;42:182-191.


Subject(s)
Acetylcholinesterase/chemistry , Galantamine/chemistry , Torpedo/metabolism , Alzheimer Disease/drug therapy , Animals , Binding Sites , Cholinesterase Inhibitors/chemistry , Crystallization , Crystallography, X-Ray , Cyclohexanes/chemistry , Cyclohexenes , Drug Design , Galantamine/therapeutic use , Models, Molecular , Nootropic Agents/chemistry , Nootropic Agents/therapeutic use , Protein Conformation , Structure-Activity Relationship
10.
Biochemistry ; 38(18): 5714-9, 1999 May 04.
Article in English | MEDLINE | ID: mdl-10231521

ABSTRACT

The crystal structure of Torpedo californica (Tc) acetylcholinesterase (AChE) carbamoylated by the physostigmine analogue 8-(cis-2,6-dimethylmorpholino)octylcarbamoyleseroline (MF268) is reported at 2.7 A resolution. In the X-ray structure, the dimethylmorpholinooctylcarbamic moiety of MF268 is covalently bound to the catalytic serine, which is located at the bottom of a long and narrow gorge. The alkyl chain of the inhibitor fills the upper part of the gorge, blocking the entrance of the active site. This prevents eseroline, the leaving group of the carbamoylation process, from exiting through this path. Surprisingly, the relatively bulky eseroline is not found in the crystal structure, thus implying the existence of an alternative route for its clearance. This represents indirect evidence that a "back door" opening may occur and shows that the release of products via a "back door" is a likely alternative for this enzyme. However, its relevance as far as the mechanism of substrate hydrolysis is concerned needs to be established. This study suggests that the use of properly designed acylating inhibitors, which can block the entrance of catalytic sites, may be exploited as a general approach for investigating the existence of "back doors" for the clearance of products.


Subject(s)
Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Carbamates/chemistry , Carbamates/metabolism , Animals , Binding Sites , Catalysis , Choline/metabolism , Cholinesterase Inhibitors/chemistry , Crystallization , Crystallography, X-Ray , Decamethonium Compounds/chemistry , Enzyme Stability , Hydrolysis , Macromolecular Substances , Models, Molecular , Morpholines/chemistry , Neuromuscular Depolarizing Agents/chemistry , Protein Conformation , Torpedo
11.
J Biol Chem ; 272(3): 1811-6, 1997 Jan 17.
Article in English | MEDLINE | ID: mdl-8999865

ABSTRACT

A wide variety of important biological processes, including both the formation and dissolution of blood clots, depend on specific cleavage of individual target proteins by serine proteases. For example, tissue type plasminogen activator (t-PA), a trypsin-like enzyme that catalyzes the rate-limiting step of the endogenous fibrinolytic cascade, has only one known substrate in vivo, a single peptide bond (Arg561-Val562) in the proenzyme plasminogen. We have previously suggested that the specificity of t-PA for plasminogen is mediated in part by direct protein-protein interactions between the protease domain of t-PA and plasminogen that are distinct from those occurring within t-PA's active site. We demonstrate in this study that residues 420-423 of t-PA, which form a fully solvent-exposed, hydrophobic region of a surface loop mapping near one edge of the active site of t-PA, form, or are essential for the integrity of, an important, secondary site of interaction between t-PA and plasminogen that significantly modulates the rate of plasminogen activation in the absence, but not the presence, of fibrin. Identification of this secondary site of interaction between t-PA and plasminogen provides new insight into molecular details of the evolution of stringent substrate specificity by t-PA and suggests a novel strategy to enhance the fibrin dependence of plasminogen activation by t-PA. While the activity of wild type t-PA is stimulated by fibrin by a factor of approximately 650, the activity of two variants characterized in this study, t-PA/R275E,P422G and t-PA/R275E,P422E, is stimulated by a factor of approximately 39,000 or 61,000, respectively. It is therefore possible that, compared with wild type t-PA, the two variants would display enhanced "clot selectivity" in vivo due to reduced activity in the circulation but full activity at a site of fibrin deposition.


Subject(s)
Plasminogen/metabolism , Tissue Plasminogen Activator/metabolism , Animals , COS Cells , Catalysis , Fibrin/metabolism , Kinetics , Mutagenesis, Site-Directed , Plasminogen Activator Inhibitor 1/pharmacology , Substrate Specificity , Tissue Plasminogen Activator/antagonists & inhibitors , Tissue Plasminogen Activator/chemistry , Tissue Plasminogen Activator/genetics
12.
Biochim Biophys Acta ; 1343(1): 41-50, 1997 Nov 14.
Article in English | MEDLINE | ID: mdl-9428657

ABSTRACT

Heptylphysostigmine is in advanced clinical trial as a drug for Alzheimer's disease. 8-Morpholinooctylphysostigmine and 8-(cis-2,6-dimethylmorpholino)octylphysostigmine are currently undergoing pre-clinical evaluation. The mechanism of action of these compounds in the inhibition of acetylcholinesterase has been investigated. All the examined compounds display non competitive-like kinetics of inhibition. There are no reversible components in the observed inhibition: the whole inhibitory effect is due to the time-dependent pseudo-irreversible carbamylation of the active site. Yet the observed time course of the inhibition does not match a simple second order kinetics. An influence of the quaternary structure of the enzyme on the more complex kinetics of carbamylation is hypothesized. Reactivation experiments on the inhibited enzyme show long lasting inhibitory effects for these compounds. The higher duration of the anticholinesterase effect of the morpholino derivatives compared to heptylphysostigmine should provide the basis for their higher therapeutic potential.


Subject(s)
Acetylcholinesterase/metabolism , Alzheimer Disease/enzymology , Cholinesterase Inhibitors/pharmacology , Physostigmine/pharmacology , Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/therapeutic use , Humans , Kinetics , Physostigmine/analogs & derivatives , Physostigmine/therapeutic use , Substrate Specificity
13.
J Mol Biol ; 258(1): 117-35, 1996 Apr 26.
Article in English | MEDLINE | ID: mdl-8613982

ABSTRACT

Tissue-type plasminogen activator (t-PA), a multidomainal serine proteinase of the trypsin-family, catalyses the rate-limiting step in fibrinolysis, the activation of plasminogen to the fibrin-degrading proteinase plasmin. Trigonal crystals have been obtained of the recombinant catalytic domain of human-two-chain t-PA, consisting of a 17 residue A chain and the 252 residue B chain. Its X-ray crystal structure has been solved applying Patterson and isomorphous replacement methods, and has been crystallographically refined to an R-value of 0.184 at 2.3 A resolution. The chain fold, active-site geometry and Ile276-Asp477 salt bridge are similar to that observed for trypsin. A few surface-located insertion loops differ significantly, however. The disulfide bridge Cys315-Cys384, practically unique to the plasminogen activators, is incorporated without drastic conformational changes as the insertion loop preceding Cys384 makes a bulge on the molecular surface. The unique basic insertion loop Lys296-Arg304 flanking the primed subsites, which has been shown to be of importance for PAI-1 binding and for fibrin specificity, is partially disordered; it can therefore freely adapt to proteins docking to the active site. The S1 pocket of t-PA is almost identical to that of trypsin, whereas the S2 site is considerably reduced in size by the imposing Tyr368 side-chain, in agreement with the measured preference for P1 Arg and P2 Gly residues. The neighbouring S3-S4 hydrophobic groove is mainly hydrophobic in nature. The structure of the proteinase domain of two-chain t-PA suggests that the formation of a salt bridge between Lys429 and Asp477 may contribute to the unusually high catalytic activity of single-chain t-PA, thus stabilizing the catalytically active conformation without unmasking the Ile276 amino terminus. Modeling studies show that the covalently bound kringle 2 domain in full-length t-PA could interact with an extended hydrophobic groove in the catalytic domain; in such a docking geometry its "lysine binding site" and the "fibrin binding patch" of the catalytic domain are in close proximity.


Subject(s)
Protein Structure, Tertiary , Tissue Plasminogen Activator/chemistry , Amino Acid Sequence , Binding Sites , Catalysis , Crystallography, X-Ray , Humans , Molecular Sequence Data , Recombinant Proteins/chemistry , Sequence Alignment , Sequence Deletion , Tissue Plasminogen Activator/genetics
14.
EMBO J ; 14(21): 5149-57, 1995 Nov 01.
Article in English | MEDLINE | ID: mdl-7489704

ABSTRACT

Rhodniin is a highly specific inhibitor of thrombin isolated from the assassin bug Rhodnius prolixus. The 2.6 Angstrum crystal structure of the non-covalent complex between recombinant rhodniin and bovine alpha-thrombin reveals that the two Kazal-type domains of rhodniin bind to different sites of thrombin. The amino-terminal domain binds in a substrate-like manner to the narrow active-site cleft of thrombin; the imidazole group of the P1 His residue extends into the S1 pocket to form favourable hydrogen/ionic bonds with Asp189 at its bottom, and additionally with Glu192 at its entrance. The carboxy-terminal domain, whose distorted reactive-site loop cannot adopt the canonical conformation, docks to the fibrinogen recognition exosite via extensive electrostatic interactions. The rather acidic polypeptide linking the two domains is displaced from the thrombin surface, with none of its residues involved in direct salt bridges with thrombin. The tight (Ki = 2 x 10(-13) M) binding of rhodniin to thrombin is the result of the sum of steric and charge complementarity of the amino-terminal domain towards the active-site cleft, and of the electrostatic interactions between the carboxy-terminal domain and the exosite.


Subject(s)
Insect Hormones/chemistry , Insect Proteins , Rhodnius/metabolism , Serine Proteinase Inhibitors/chemistry , Thrombin/antagonists & inhibitors , Amino Acid Sequence , Animals , Binding Sites , Cattle , Crystallization , Hirudins/chemistry , Molecular Sequence Data , Protein Conformation , Sequence Alignment
15.
Carbohydr Res ; 276(2): 401-8, 1995 Oct 23.
Article in English | MEDLINE | ID: mdl-8542607

ABSTRACT

Several samples of oversulfated chondroitin and dermatan were obtained by chemical sulfation and by SAX-HPLC enrichment. The starting products and oversulfated products were tested as potential inhibitors of human leukocyte elastase, an enzyme hypothesized to be involved in the etiology of diseases such as emphysema, atherosclerosis, and rheumatoid arthritis. Chemical oversulfation (SO3H/COOH 1.6-3.2), preferentially occurring at C-6 of galactosamine residues, was found generally to increase the inhibitory power on elastase. Chemically oversulfated galactosaminoglycans thus have potential as therapeutic agents, considering that they produce non-significant effects on the hemocoagulative system. Two naturally oversulfated dermatans sulfate (SO3H/COOH ca. 1.2), mainly oversulfated at C-2 of iduronic acid residues, showed comparatively higher anticoagulant activity (in the HC-II mediated thrombin inhibition test).


Subject(s)
Chondroitin Sulfates/pharmacology , Dermatan Sulfate/pharmacology , Enzyme Inhibitors/pharmacology , Pancreatic Elastase/antagonists & inhibitors , Polysaccharides/pharmacology , Animals , Blood Coagulation/drug effects , Carbohydrate Sequence , Cartilage/chemistry , Cattle , Chondroitin Sulfates/metabolism , Dermatan Sulfate/metabolism , Enzyme Inhibitors/chemistry , Humans , Leukocyte Elastase , Leukocytes/enzymology , Molecular Sequence Data , Molecular Structure , Polysaccharides/metabolism , Sharks , Sulfates/metabolism , Sulfur Oxides/metabolism
16.
Int J Biol Macromol ; 17(3-4): 219-26, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7577821

ABSTRACT

The crystal and molecular structure of 2-sulfamino-2-deoxy-alpha-D-glucopyranose has been determined by direct methods. The crystal belongs to the space group P2(1)2(1)2(1) and has unit cell dimensions a = 7.713 A, b = 9.390 A and c = 17.222 A. The sugar ring has the expected conformation (4C1) and the geometry of the N-sulfate moiety is comparable with that found in previous investigations of monosaccharide O-sulfates. The sodium ion is octahedrally coordinated involving one ring oxygen, two hydroxyls, one sulfate oxygen and two water oxygens.


Subject(s)
Glucosamine/analogs & derivatives , Monosaccharides/chemistry , Sulfuric Acid Esters/chemistry , Carbohydrate Conformation , Crystallography, X-Ray , Glucosamine/chemistry , Hydrogen Bonding , Models, Molecular , Structure-Activity Relationship
18.
Glycobiology ; 4(2): 151-63, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8054715

ABSTRACT

The three-dimensional structures of the 2-, 3-, 4- and 6-monosulphates of methyl alpha-D-galactopyranoside have been determined by X-ray crystallography; the first two as the sodium salt, the third as both the sodium and potassium salts, and the fourth as a potassium salt. These represent the principal sulphated monomers of the carrageenan polysaccharides. The results extend our knowledge of the stereochemical features, such as ring conformation, sulphate geometry, hydrogen bonding and cation co-ordination, which characterize sulphated monosaccharides. The stereochemical data have been used to derive a mean geometry of the O-sulphate group and a set of force constants for use in molecular mechanics calculations on sulphated monosaccharides. These may be used in an extrapolation of the populations of stable conformers of related oligo- and polysaccharides.


Subject(s)
Carrageenan/chemistry , Galactose/analogs & derivatives , Carbohydrate Conformation , Crystallography, X-Ray/methods , Galactose/chemistry , Hydrogen Bonding , Models, Molecular
19.
Biopolymers ; 34(4): 457-62, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8186359

ABSTRACT

1H-NMR and molecular dynamics simulations in vacuo and in water of (1-->4)-alpha-D-galacturono-disaccharide were performed. The results of the molecular dynamics simulations showed that the molecule fluctuates between two conformations characterized by different values of torsion angles around the glycosidic linkage and two different intramolecular hydrogen bonds. When these conformations are extrapolated to a regular polymeric structure, they generate pectic acid compatible with a 2(1)- or a right-handed 3(1)-helix.


Subject(s)
Pectins/chemistry , Biopolymers/chemistry , Carbohydrate Conformation , Carbohydrate Sequence , Disaccharides/chemistry , Magnetic Resonance Spectroscopy , Molecular Sequence Data , Solutions , Thermodynamics
20.
Acta Crystallogr C ; 48 ( Pt 1): 81-3, 1992 Jan 15.
Article in English | MEDLINE | ID: mdl-1605931

ABSTRACT

C8H10N2O3, Mr = 182.18, monoclinic, P2(1), a = 6.6405 (7), b = 7.9493 (9), c = 8.3662 (9) A, beta = 103.07 (1) degrees, V = 430.18 (8) A3, Z = 2, Dx = 1.41 Mg m-3, lambda (Cu K alpha) = 1.54184 A, mu = 0.879 mm-1, F(000) = 192, T = 298 K, R = 0.037 for 1247 reflections with Fo greater than or equal to 4 sigma (Fo). The configuration at C7 is S. The pyrimidine-2,4-dione ring is nearly planar [r.m.s. deviation: 0.010 (8) A] and is antiperiplanar with respect to the epoxide ring. This arrangement is stabilized by intermolecular C-H ... O interactions.


Subject(s)
African Swine Fever Virus/drug effects , Antiviral Agents/chemistry , Pyrimidinones/chemistry , Crystallization , Models, Chemical , Molecular Conformation , Pyrimidinones/pharmacology , X-Ray Diffraction
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