CONFORMATION OF A82846B, A GLYCOPEPTIDE ANTIBIOTIC, COMPLEXED WITH ITS CELL-WALL FRAGMENT - AN ASYMMETRIC HOMODIMER DETERMINED USING NMR-SPECTROSCOPY

Proton NMR assignments were determined for the asymmetric dimer comple x of A82846B with the pentapeptide cell-wall fragment, A total of 683 experimental constraints, both distance and dihedral, were collected f rom NOESY and COSY data sets, From these constraints, a total of 80 st ructures were calculated using standard X-PLOR protocols. These struct ures were subsequently refined using the full CHARMm potential and the addition of water molecules in the calculation. The CHARMm structures occupied more conformational space than did the X-PLOR structures and were utilized for the structure analysis. From the structures, a uniq ue set of interactions for the dALA-5 carboxylate pocket was observed, having backbone amides from residues 2 and 3 hydrogen bonding one car boxylate oxygen while amide 4 and the side chain amide from Asn-3 hydr ogen bond the other oxygen. Also, near the N-terminal region of the li gand, the GGLU-2's carboxylate forms a hydrogen bond with the asymmetr ic disaccharide dyad, which helps to define the interactions seen for this part of the ligand.