Showing papers by "Anne Imberty published in 1991"

Recent Advances in Knowledge of Starch Structure

Abstract: Three dimensional models of crystalline zones and amorphous branching zones of starch granules are reviewed. In crystallites of both A and B starch, double helices are found in pairs, and all chains are packed in parallel arrays. The pairing of double helices is identical in both polymorphs and corresponds to the interaction between double helices that has the lowest energy. The differences between A and B starch arise from water content and the manner in which these pairs are packed in the respective crystals. A transition from B starch to the A form can be accomplished by rearrangement of the pairs of double helices. The 1–6 linked amylopectin branch points occur in amorphous regions, but actually promote the formation of ordered double helices.

Molecular modelling of protein-carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A

Abstract: A general procedure is described for addressing the computer simulation of protein-carbohydrate interactions. First, a molecular mechanical force field capable of performing conformational analysis of oligosaccharides has been derived by the addition of new parameters to the Tripos force field; it is also compatible with the simulation of protein. Second, a docking procedure which allows for a systematic exploration of the orientations and positions of a ligand into a protein cavity has been designed. This so-called 'crankshaft' method uses rotations and variations about/of virtual bonds connecting, via dummy atoms, the ligand to the protein binding site. Third, calculation of the relative stability of protein ligand complexes is performed. This strategy has been applied to search for all favourable interactions occurring between a lectin [concanavalin A (ConA)] and methyl alpha-D-mannopyranoside or methyl alpha-D-glucopyranoside. For each monosaccharide, different stable orientations and positions within the binding site can be distinguished. Among them, one corresponds to very favourable interactions, not only in terms of hydrogen bonding, but also in terms of van der Waals interactions. It corresponds precisely to the binding mode of methyl alpha-D-mannopyranoside into ConA as revealed by the 2.9 A resolution of the crystalline complex (Derewenda et al., 1989). Some implications of the present modelling study with respect to the molecular basis of the specificity of the interaction of lectins with various monosaccharides are presented.

Conformational behavior of sucrose and its deoxy analog in water as determined by NMR and molecular modeling

Abstract: The conformational behavior of aqueous sucrose and its 2-deoxy analogue were studied by NMR and computerized molecular modeling. 'H steady-state NOE and NOESY data are reported along with long-range W-'H coupling constants. In modeling calculations, a full force field energy minimization was used to obtain the initial residue geometry, followed by a rigid residue approximation in which the glycosidic dihedral angles and the methoxyl group orientations are varied. Theoretical steady-state NOEs are calculated by a full spin relaxation matrix method, and 3JC-H data are correlated with the glycosidic torsional angle. The data do not support a single conformation model, and only conformational averaging can give a good agreement between theoretical and experimental data. The inclusion of hydrogen bonding in the force field does not affect the statistical weights of calculated NOEs, and the similar values of observed NOEs for sucrose and the 2-deoxy analogue argue against the importance of hydrogen bonding in sucrose conformation. Introduction The molecular conformation in crystalline sucrose is known unambiguously through X-ray' and neutron diffraction2 studies. However, the conformational behavior of sucrose in aqueous solution is still controversial, despite numerous experimentalf" and model i r~g~r '~ studies. In most of those e f f o r t ~ , ~ J ~ ' ~ sucrose was assumed to be nearly spherical, similar to its shape in crystalline sucrose, and quite rigid. However, when the crystal structures of sucrase,'J sucrose-salt comple~es , '~J~ and oligosaccharides that contain sucrosyl residueslbZ are examined, the (1 2) glycosidic linkages between a-glucopyranose and 0-fructofuranose exhibit wide ranges (see Table I). Recent molecular mechanics and dynamics s t ~ d i e s ~ ~ v ~ ~ identified three low-energy conformations for sucrose, providing further support for the concept of flexible linkages in this disaccharide. Besides the flexibility of sucrose, another controversy is the persistence in solution of the 0-2g-O-If and 0-5g-O-6f hydrogen bonds found in the crystal. Mathlouti et al.3-S interpreted X-ray and Raman data to show that the number of intramolecular hydrogen bonds depends on the concentration of sucrose, with no hydrogen bonding at low concentrations. Bock and Lemieux"J2 argued, supported by modeling and detailed I3C TI and NOE measurements, that dilute aqueous sucrose has one intramolecular hydrogen bond. Finally, based on their N M R study of sucrose in DMSO, Christofides and Davies6v7 suggested that two intramolecular hydrogen bonds, namely 0-2g-0-1 f and 0-2g-0-3f, compete with each other. Because of these observations and a report that the crystalline conformation cannot account for all of the N M R data,I0 we decided that further study was needed. Interpreting the solution behavior of sucrose from N M R data without an assumption of rigid conformation is an ambitious task, since NMR parameters reflect only a "virtual" conformat i~n .~~ Recently, Cumming and Carverz6 combined N M R data with results from computerized molecular modeling that accommodates conformational flexibility. Further analyses of various diand trisaccharides have mostly used NOE value^^'-^^ although constants from coupling through the glycosidic linkage were also This modeling procedure is used in the present work. The extent of intramolecular hydrogen bonding is probed in a parallel study of 2-deoxysucrose, a compound that cannot form the 0-1f-O-2g hydrogen bond. Also, the 'Service RMN du DEpartement de Chimie. * Laboratoire de Physicochimie des MacromolEcules. 1 Laboratoire Beghin-Say. E.S.C.I.L. Laboratoire de Chimie Organique 11. E.S.C.I.L. potential energy functions were used with and without a term for hydrogen bonding. (1) Hanson, J. C.; Sieker, L. C.; Jensen, L. H. Acta Crystallogr. 1973, B29, (2) Brown, G. M.; Levy, H. A.; Acta Crystallogr. 1973, 829, 790-791. (3) Mathlouthi, M. Carbohydr. Res. 1981, 91, 113-123. (4) Mathlouthi, M.; Luu, D. V. Carbohydr. Res. 1980,81, 203-212. (5) Mathlouthi, M.; Luu, C.; Meffroy-Biget, A. M.; Luu, D. V. Carbohydr. (6) Christofides, J. C.; Davis, D. B. J. Chem. Soc., Chem. Commun. 1985, (7) Davies, D. B.; Christofides, J. C. Carbohydr. Res. 1987,163,269-274. ( 8 ) McCain, D. C.; Markley, J. L. Carbohydr. Res. 1986, 152, 73-80. (9) McCain, D. C.; Markley, J. L. J . Am. Chem. Soc. 1986, 108, (10) Mulloy, B.; Frenkiel, T. A.; Davis, D. B. Carbohydr. Res. 1988,184, (11) Lemieux, R. U.; Bock, K. Jpn. J. , Antibiot. 1979, XXXII Suppl., (12) Bock, K.; Lemieux, R. U. Carbohydr. Res. 1982, 100, 63-74. (1 3) Giacomini, M.; Pullman, B.; Maigret, B. Theor. Chim. Acta 1970, (14) Accorsi, C. A.; Bellucci, F.; Bertolasi, V.; Ferretti, V.; Gilli, G. (15) Accorsi, C. A.; Bertolasi, V.; Ferretti, V.; Gilli, G. Carbohydr. Res. (16) Berman, H. M. Acta Crystallogr. 1970, 826, 290-299. (17) Rohrer, D. C. Acta Crystallogr. 1972, B28, 425-433. (18) Jeffrey, G. A.; Park, Y. J. Acta Crystallonr. 1972, B28, 257-261. 797-808. Res. 1980, 81, 213-233.

Data bank of three-dimensional structures of disaccharides: Part II, N-acetyllactosaminic type N-glycans. Comparison with the crystal structure of a biantennary octasaccharide.

Abstract: Conformational energy maps and descriptions of structures at the local minima are presented for the following fragments found inN-acetyllactosaminic type glycans of N-glycoproteins: GlcNAcβ(1–2)Man, GlcNAcβ(1–4)Man, GlcNAcβ(1–6)Man, Galβ(1–4)GlcNAc, GlcNAcβ(1–3)Gal, Fucα(1–6)GlcNAc, Fucα(1–3)GlcNAc, Xylβ(1–2)Man, Galβ(1–3)GlcNAc and GlcNAcβ(1–6)Gal. These results are the second part of a data bank on glycoprotein moieties; five disaccharides found in oligomannose type N-glycans were analysed earlier (Imbertyet al., 1990,Glycoconjugate J7:27–54). In the present study, three to seven minima are found for each dimer. Conformations of disaccharide fragments found in the crystal structure of the complex of a biantennary octasaccharide withLathyrus ochrus lectin are plotted on these energy maps. While the observed conformations are at predicted minima, they are not always at the minimum predicted to have the lowest energy. Further, not all observed conformations are stabilized by the exo-anomeric effect. We conclude that these oligosaccharides are highly flexible.