In all organisms adenylate kinases (Adks) play a vital role in cellular energy metabolism and nucleic acid synthesis. Due to differences in catalytic properties between the Adks found in prokayotes and in the cytoplasm of eukaryotes, there is interest in targeting this enzyme for new drugs therapies against infectious bacterial agents. Here we report the 2.1 Å resolution crystal structure for the 220-residue Adk from Burkholderia pseudomallei (BpAdk), the etiological agent responsible for the infectious disease meliodosis. The general structure of apo BpAdk is similar to other Adk structures, composed of a CORE subdomain with peripheral ATP-binding (ATPbd) and LID subdomains. The two molecules in the asymmetric unit have significantly different conformations, with a backbone RMSD of 1.46 Å. These two BpAdk conformations may represent ‘open’ Adk sub-states along the preferential pathway to the ‘closed’ substrate-bound state.
Revised: July 22, 2010 |
Published: April 16, 2010
Citation
Buchko G.W., H. Robinson, J. Abendroth, B.L. Staker, and P.J. Myler. 2010.Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): Profound asymmetry in the crystal structure of the ‘open’ state.Biochemical and Biophysical Research Communications 394, no. 4:1012-1017. PNWD-SA-8859.