X-ray structures of the Dictyostelium discoideum myosin motor domain with six non-nucleotide analogs

The three-dimensional structures of the truncated myosin head from Dictyost elium discoideum myosin II complexed with dinitrophenylaminoethyl-, dinitro phenylaminopropyl-, o--nitrophenylaminoethyl-, m-nitrophenylaminoethyl-, p- nitrophenylaminoethyl-, and o-nitrophenyl-N-methyl-aminoethyl-diphosphate . beryllium fluoride have been determined to better than 2.3-Angstrom resolu tion. The structure of the protein and nucleotide binding pocket in these c omplexes is very similar to that of S1dC . ADP . BeFx (Fisher, A. J., Smith , C. A., Thoden, J., Smith, R,, Sutoh, K., Holden, H. M., and Rayment, I. ( 1995) Biochemistry 34, 8960-8972). The position of the triphosphate-like mo iety is essentially identical in all complexes. Furthermore, the alkyl-amin o group plays the same role as the ribose by linking the triphosphate to th e adenine binding pocket; however, none of the phenyl groups lie in the sam e position as adenine in S1dC . MgADP . BeFx, even though several of these nucleotide analogs are functionally equivalent to ATP, Rather the former lo cation of adenine is occupied by water in the nanolog complexes, and the ph enyl groups are organized in a manner that attempts to optimize their hydro gen bonding interactions with this constellation of solvent molecules. A co mparison of the kinetic and structural properties of the nanologs relative to ATP suggests that the ability of a substrate to sustain tension and to g enerate movement correlates with a well defined interaction with the active site water structure observed in S1dC . MgADP . BeFx.