A crystallization strategy termed 'microseed matrix screening' is described where the optimal conditions for nucleation versus extended lattice growth are not compatible. This method is an extension of conventional seeding techniques in which microseeds from the nucleation step are systematically seeded into new conditions where all components of the drop are allowed to vary to screen for subsequent growth of well ordered specimens. The structure of a crystal form of yeast cytosine deaminase produced by streak-seeding using a single condition for both nucleation and growth is compared with the structure of a related crystal form produced by separating nucleation and growth conditions. The resulting structural comparison demonstrates that differential chelation patterns of cations by acidic surface residues of proteins within crystal lattice contacts is a critical parameter of crystal nucleation and growth.