The structure of Methylcob(III)alamin in aqueous solution - A water molecule as structuring element of the nucleotide loop

The solution structure of methylcob(III)alamin (MeCbl; 3), a natural organo metallic corrinoid-B-12 cofactor whose crystal structure was published in 1 985, was established by NMR-spectroscopic analyses of 3 in aqueous solution . The full set of unambiguously assigned H-1, C-13, and amide N-15 signals was consistent with identical constitutional and configurational properties of 3 in solution and in the crystal. Specifically investigated were the co nformational characteristics of 3 in solution, in particular of its unique Co-coordinating nucleotide moiety. An extensive set of NOE-derived distance constraints was acquired for this purpose, and of angle constraints, based on three-bond coupling constants. These data were used to calculate the so lution structure of 3. Our data revealed that the conformation of the nucle otide loop of 3 differs significantly in aqueous solution and in the crysta lline state and indicated the presence of a specific H2O molecule 'bound' v ia cooperative H-bonds to three H-bonding functionalities of the nucleotide loop. The observed conformational differences are attributed to structurin g contributors to the nucleotide conformation that differ in solution and i n the crystal. Most of these can be assigned to H2O molecules, whose positi on in the crystal is controlled, in part, by the specific crystal packing.