Molecular modelling of acarviosine, the pseudo- disaccharide moiety of acarbose, and other inhibitors of alpha-amylases

Raimbaud, Eric; Buléon, Alain; Pérez, Serge

doi:10.1016/0008-6215(92)85084-d

Cited by 17 publications

(18 citation statements)

References 17 publications

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“…The former map has only three minima below 8 kcal/mol (Table I), and is globally close to that previously found for methyl a-S-acarviosinide. 20 Its global minimum, an S conformer, is located at f,c 5 259°,-40°, with significantly higher second and third minima at f,c 5 17°,26°and f,c 5 262°,166°, an R and an S structure, respectively. These minima are found in the region containing the main local maltose analogue minima, 20 which in turn are close to the minima of a-maltose.…”

Section: Results and Discussion Conformational Analysis Of Methyl A-amentioning

confidence: 99%

“…Two sets of reverseclockwise orientations were necessary for the nonreducing ring of the uncharged methyl a-acarviosinides, since a C-3 A -C-2 A -O-2 A -H(O-2) A torsional angle of 60°yields an interring hydrogen bond that cannot occur in the protonated form. In the valiemine moiety, three sets of stable C-7 A -C-5 A -C-6 A -O-6 A torsional angles were considered as before 20 with values of approximately 2130°, 210°, and 100°. Following docking, torsion angles close to these values were subdivided into groups x 1 , x 2 , and x 3 , respectively, the relative position of the OH-6 A group to the valiemine ring being analogous to the related gg, gt, and tg conformers of maltose.…”

Section: Conformational Analysis Of Methyl A-acarviosinidesmentioning

confidence: 99%

“…Given the inability of MM3(92) to maintain the stereochemistry around N-4 B to generate complete and independent sets of R and S structures of uncharged methyl a-acarviosinide, the initial structures used in docking were regenerated from MM2(85) results, 20 their energies being evaluated with MM3(92) at e 5 4.0.…”

Section: Conformational Analysis Of Methyl A-acarviosinidesmentioning

confidence: 99%

“…Docking simulations were made on each initial structure of the optimized monosaccharide and monosaccharide analogue structures, as well as on five methyl a-R-and three methyl a-S-acarviosinide conformers from the MM2(85) study, 20 and of seven protonated methyl a-acarviosinide conformers, the local minima 8 kcal/mol or less above the global minima given by MM3(92). Following docking, cluster analysis of all structures generated for a single compound was performed.…”

Section: Docking Simulationsmentioning

confidence: 99%

“…9,11 Conformational studies of 4-thiomaltose and uncharged acarviosine, the pseudodisaccharide moiety of acarbose, showed that these glucosidase inhibitors share with maltose a common conformational space with very similar low-energy minima. 20 On the other hand, significant pH-dependent conformational differences occur around the amino linkage of acarbose. 21 Protein-substrate interactions can be modeled by several methods 22 .…”

Section: Introductionmentioning

confidence: 99%

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Automated docking of monosaccharide substrates and analogues and methyl α-Acarviosinide in the glucoamylase active site

1997

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Glucoamylase is an important industrial glucohydrolase with a large specificity range. To investigate its interaction with the monosaccharides D-glucose, D-mannose, and D-galactose and with the substrate analogues 1-deoxynojirimycin, D-glucono-1,5-lactone, and methyl alpha-acarviosinide, MM3(92)-optimized structures were docked into its active site using AutoDock 2.1. The results were compared to structures of glucoamylase complexes obtained by protein crystallography. Charged forms of some substrate analogues were also docked to assess the degree of protonation possessed by glucoamylase inhibitors. Many forms of methyl alpha-acarviosinide were conformationally mapped by using MM3(92), characterizing the conformational pH dependence found for the acarbose family of glucosidase inhibitors. Their significant conformers, representing the most common states of the inhibitor, were used as initial structures for docking. This constitutes a new approach for the exploration of binding modes of carbohydrate chains. Docking results differ slightly from x-ray crystallographic data, the difference being of the order of the crystallographic error. The estimated energetic interactions, even though agreeing in some cases with experimental binding kinetics, are only qualitative due to the large approximations made by AutoDock force field.

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Section: Results and Discussion Conformational Analysis Of Methyl A-amentioning

confidence: 99%

Section: Conformational Analysis Of Methyl A-acarviosinidesmentioning

confidence: 99%

Section: Conformational Analysis Of Methyl A-acarviosinidesmentioning

confidence: 99%

Section: Docking Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Automated docking of monosaccharide substrates and analogues and methyl α-Acarviosinide in the glucoamylase active site

1997

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Amylose chain behavior in an interacting context I. Influence of a nonchair ring on the maltose conformations

André¹,

Buléon²,

Tran³

et al. 1998

Biopolymers

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In the presence of steric constraints, flexible forms, i.e., skew (S), boat (B) or half-boat ( H ) , were evoked ,from experimental data and conformarional analyses by molecular mechanics calculations for glucopyranose rings of umylose fragments. This important case, occurring, for example, in amylose-amylase complexes, requires careful analysis of these flexible ring forms prior to any further conformational study. The influence of a nonchair (flexible) form on the maltose conformation is systematically evaluated, with an appropriate strategy using 'semirelaxed" maps and comparing them with those obtained from already known chair-chair ('C1-'C1) maps. Therefore, new low-energy maltose conformations are described and classijiedfrom flexible-chair and chair-flexible maps. These conformations are well dispersed inside signijicantly larger contours in the (p. +) projection. In a second stage, the consequence of these jlexible ring forms is discussed in terms of amylose propagation apart from these new maltose conformations. Two propagation parameters are defined (r. Q), related to the local curvature of the chain and the relative orientation ofthe two mean ring planes. Low-energy conformations of4Cl-'Cl maltose have almost the same curvature between the two rings, whereas their relative orientations have well-identified D values. On the contrary, the presence of one jlexible conformation considerably increases the variation range of both propagation parameters. Thus, new low-energy conformations allow local curvatures yielding from almost perpendicular to linear pairs of glucopyranose rings with relative orientation covering about threefourths of the total domain. This description is essential to understand amylose conformations in catalytic site and subsites of the amylases.

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The Conformational Behaviour of Non-Hydrolizable Lactose Analogues: The Thioglycoside, Carbaglycoside, and Carba-Iminoglycoside Cases

et al. 2000

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Molecular modelling of acarviosine, the pseudo- disaccharide moiety of acarbose, and other inhibitors of alpha-amylases

Cited by 17 publications

References 17 publications

Automated docking of monosaccharide substrates and analogues and methyl α-Acarviosinide in the glucoamylase active site

Automated docking of monosaccharide substrates and analogues and methyl α-Acarviosinide in the glucoamylase active site

Amylose chain behavior in an interacting context I. Influence of a nonchair ring on the maltose conformations

The Conformational Behaviour of Non-Hydrolizable Lactose Analogues: The Thioglycoside, Carbaglycoside, and Carba-Iminoglycoside Cases

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