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Three‐dimensional structure of cyclic antibiotic teicoplanin aglycone using NMR distance and dihedral angle restraints in a DMSO solvation model
Author(s) -
Gonnella Nina C.,
Grinberg Nelu,
Mcloughlin Mark,
Choudhary Om,
Fandrick Keith,
Ma Shengli
Publication year - 2015
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.4279
Subject(s) - chemistry , dihedral angle , solvation , aglycone , computational chemistry , teicoplanin , nuclear magnetic resonance , stereochemistry , organic chemistry , molecule , hydrogen bond , vancomycin , bacteria , glycoside , biology , staphylococcus aureus , physics , genetics
The three‐dimensional solution conformation of teicoplanin aglycone was determined using NMR spectroscopy. A combination of NOE and dihedral angle restraints in a DMSO solvation model was used to calculate an ensemble of structures having a root mean square deviation of 0.17 Å. The structures were generated using systematic searches of conformational space for optimal satisfaction of distance and dihedral angle restraints. Comparison of the NMR‐derived structure of teicoplanin aglycone with the X‐ray structure of a teicoplanin aglycone analog revealed a common backbone conformation with deviation of two aromatic side chain substituents. Experimentally determined backbone 13 C chemical shifts showed good agreement with those computed at the density functional level of theory, providing a cross validation of the backbone conformation. The flexible portion of the molecule was consistent with the region that changes conformation to accommodate protein binding. The results showed that a hydrogen‐bonded DMSO molecule in combination with NMR‐derived restraints together enabled calculation of structures that satisfied experimental data. Copyright © 2015 John Wiley & Sons, Ltd.