SWIVELING-DOMAIN MECHANISM FOR ENZYMATIC PHOSPHOTRANSFER BETWEEN REMOTE REACTION SITES

The crystal structure of pyruvate phosphate dikinase, a histidyl multi phosphotransfer enzyme that synthesizes adenosine triphosphate, reveal s a three-domain molecule in which the phosphohistidine domain is flan ked by the nucleotide and the phosphoenolpyruvate/pyruvate domains, wi th the two substrate binding sites approximate to 45 Angstrom apart, T he modes of substrate binding have been deduced by analogy to D-Ala-D- Ala ligase and to pyruvate kinase. Coupling between the two remote act ive sites is facilitated by two conformational states of the phosphohi stidine domain, While the crystal structure represents the state of in teraction with the nucleotide, the second state is achieved by swiveli ng around two flexible peptide linkers. This dramatic conformational t ransition brings the phosphocarrier residue in close proximity to phos phoenolpyruvate/pyruvate. The swiveling-domain paradigm provides an ef fective mechanism for communication in complex multidomain/multiactive site proteins.