The switch between two conformations of adenylate kinase

Crystalline adenylate kinase from porcine muscle cytosol can assume two interconvertible structures. Here, we report the refined structure of crystal form B at 3.3 A resolution and compare it with crystal form A. Crystal forms A and B can be interconverted by protonation and deprotonation of His36, which is located deep in the active center cleft. The changes concern the molecular packing as well as the polypeptide chain conformation. On conversion from crystal form A to B, the N-terminal alpha-helix unwinds, the active center cleft opens to some extent and the nucleotide-binding glycine-rich loop 15-22 at the active center is detached from the bulk protein. This loop has counterparts in various important mononucleotide-binding proteins and is known to bind a phosphoryl group in adenylate kinase and in the oncogenic ras proteins. It is most likely involved in the phosphoryl transfer and the concomitant conformational changes. it is suggested that the two observed conformations are relevant for enzyme action in solution: they represent two of a series of three known snapshots depicting the enzyme during the substrate binding process.