title: Conformational study in water by NMR and molecular modeling of cyclic glutamic acid analogues as probes of vitamin K dependent carboxylase.
abstract: The conformational analysis of four glutamic acid analogues containing a cyclopentyl or cyclohexyl ring, substituted in position 1 by a BOC protected amino group and a methyl ester group and in position 3 by a free carboxylate group, has been carried out in an aqueous environment, by 1H and 13C NMR spectroscopy, and molecular dynamics (MD). Their structural properties were under investigation for a structure-activity relationship analysis to determine the preferred conformation in the carboxylase active site. For each compounds, resulting conformations from NMR and MD data were analyzed and classified according to the dihedral angles chi 1 and chi 2, the distances and the spatial distribution involving charged or substituted C- and N-terminal groups. A reduced number of conformational families were found to be in qualitative agreement with NMR and MD data. A comparison between these different classes of the active and nonactive derivatives was achieved.
authors.affiliation: Université René Descartes-Paris V, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (URA 400 CNRS), Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Larue
authors.forename: J
authors.initials: J
authors.lastname: Gharbi-Benarous
authors.forename: F
authors.initials: F
authors.lastname: Archer
authors.forename: R
authors.initials: R
authors.lastname: Azerad
authors.forename: J P
authors.initials: JP
authors.lastname: Girault
mesh_terms: D000818:Animals; D019735:Carbon-Carbon Ligases; D003198:Computer Simulation; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D066298:In Vitro Techniques; D008025:Ligases / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000201:enzymology; D008958:Models, Molecular; D008968:Molecular Conformation; D015335:Molecular Probes / Q000737:chemistry; D015394:Molecular Structure; D013816:Thermodynamics
chemical_list: D015335:Molecular Probes; D018698:Glutamic Acid; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase