Molecular symmetry as an aid to geometry determination in ligand protein complexes

Dipole-dipole couplings between pairs of spin 1/2 nuclei, which can be meas ured from NMR spectra in field-ordered media, offer useful constraints on t he orientation of various fragments in molecular systems. However, the orie ntation of fragments relative to a molecule fixed reference frame is often key to complete structure determination. Here, we demonstrate that the symm etry properties of molecular complexes can aid in the definition of a refer ence frame, It is shown that a threefold rotational symmetry axis dictates the direction and symmetry of the experimentally determined order tensor fo r alpha-methyl-mannose in fast exchange among the three symmetry-related bi nding sites of mannose binding protein. This approach facilitates studies o f the geometry of the ligand in the protein-ligand complex and also may pro vide a novel route to structure determination of a homomultimeric protein. (C) 2000 Academic Press.