Molecular dynamics simulations on the complexes of glucoamylase II (471) from Asgergillus awamori var. X100 with 1-deoxynojirimycin and lentiginosine

被引:18
作者
Cardona, F
Goti, A
Brandi, A
Scarselli, M
Niccolai, N
Mangani, S
机构
[1] UNIV FLORENCE,DIPARTIMENTO CHIM ORGAN U SCHIFF,CNR,I-50121 FLORENCE,ITALY
[2] UNIV SIENA,DIPARTIMENTO BIOL MOL,SIENA,ITALY
[3] UNIV SIENA,DIPARTIMENTO CHIM,I-53100 SIENA,ITALY
关键词
glycosidase inhibitors; protein-substrate adduct; enzyme cavity; azasugar; polyhydroxylated indolizidines;
D O I
10.1007/s008940050037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Molecular dynamics (MD) simulations on the complexes of glucoamylase II (471) from Aspergillus awamori var. X100 with two powerful inhibitors, 1-deoxynojirimycin and (+)-lentiginosine, have been performed, in order to build a model for these complexes in solution and to clarify the structure-activity relationship. MD calculations were carried out for 105 ps, over a 15 Angstrom sphere centered on the inhibitors. A 8 Angstrom residue-based cut-off was used, and the calculations were performed with explicit inclusion of solvent molecules. The MD structure of the complex 1-deoxynojirimycin-glucoamylase shows only minor deviations from the available X-ray structure. The MD structure of the complex of (+)-lentiginosine-glucoamylase, obtained by docking the inhibitor into the active site, suggests us a suitable orientation for the molecule into the enzyme cavity, which can rationalize the high inhibition activity found for (+)-lentiginosine towards amyloglucosidase from A. niger.
引用
收藏
页码:249 / 260
页数:12
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