tailieunhanh - Báo cáo khoa hoc : Quaternary structure, conformational variability and global motions of phosphoglucosamine mutase

Phosphoglucosamine mutase (PNGM) is a bacterial enzyme that partici-pates in the peptidoglycan biosynthetic pathway. Recent crystal structures of PNGM from two bacterial pathogens,Bacillus anthracisandFrancisella tularensis, have revealed key structural features of this enzyme for the first time. | IFEBS Journal Quaternary structure conformational variability and global motions of phosphoglucosamine mutase Ritcha Mehra-Chaudhary1 Jacob Mick1 John J. Tanner1 2 and Lesa J. Beamer1 2 1 Biochemistry Department University of Missouri Columbia MO USA 2 Chemistry Department University of Missouri Columbia MO USA Keywords Bacillus anthracis negative cooperativity normal mode analysis phosphohexomutase small-angle X-ray scattering Correspondence L. J. Beamer Biochemistry and Chemistry Departments 117 Schweitzer Hall University of Missouri Columbia MO 65211 USA Fax 1 573 884 4812 Tel 1 573 882 6072 E-mail beamerl@ These authors contributed equally to this work Received 6 June 2011 revised 11 July 2011 accepted 12 July 2011 doi Phosphoglucosamine mutase PNGM is a bacterial enzyme that participates in the peptidoglycan biosynthetic pathway. Recent crystal structures of PNGM from two bacterial pathogens Bacillus anthracis and Francisella tularensis have revealed key structural features of this enzyme for the first time. Here we follow up on several novel findings from the crystallographic studies including the observation of a structurally conserved interface between polypeptide chains and conformational variability of the C-terminal domain. Small-angle X-ray scattering of B. anthracis PNGM shows that this protein is a dimer in solution. Comparisons of the four independent polypeptide chains from the two structures reveals conserved residues and structural changes involved in the conformational variability as well as a significant rotation of the C-terminal domain of nearly 60 between the most divergent conformers. Furthermore the fluctuation dynamics of PNGM are examined via normal mode analyses. The most mobile region of the protein is its C-terminal domain consistent with observations from the crystal structures. Large regions of correlated collective motions are identified exclusively for the dimeric state of the protein .