CRYSTAL-STRUCTURES AT 2.5 ANGSTROM RESOLUTION OF SERYL-TRANSFER-RNA SYNTHETASE COMPLEXED 2 ANALOGS OF SERYL ADENYLATE

Crystal structures of seryl-tRNA synthetase from Thermus thermophilus complexed with two different analogs of seryl adenylate have been dete rmined at 2.5 Angstrom resolution. The first complex is between the en zyme and seryl-hydroxamate-AMP (adenosine monophosphate), produced enz ymatically in the crystal from adenosine triphosphate (ATP) and serine hydroxamate, and the second is with a synthetic analog of seryl adeny late (5'-O-[N-(L-seryl)-sulfamoyl]adenosine), which is a strong inhibi tor of the enzyme. Both molecules are bound in a similar fashion by a network of hydrogen bond interactions in a deep hydrophilic cleft form ed by the antiparallel beta sheet and surrounding loops of the synthet ase catalytic domain. Four regions in the primary sequence are involve d in the interactions, including the motif 2 and 3 regions of class 2 synthetases. Apart from the specific recognition of the serine side ch ain, the interactions are likely to be similar in all class 2 syntheta ses.