Structure, function and dynamics in the mur family of bacterial cell wall ligases.
For bacteria, the structural integrity of its cell wall is of utmost importance for survival, and to this end, a rigid scaffold called peptidoglycan, comprised of sugar molecules and peptides, is synthesized and located outside the cytoplasmic membrane of the cell. Disruption of this peptidoglycan layer has for many years been a prime target for effective antibiotics, namely the penicillins and cephalosporins. Because this rigid layer is synthesized by a multi-step pathway numerous additional targets also exist that have no counterpart in the animal cell. Central to this pathway are four similar ligase enzymes, which add peptide groups to the sugar molecules, and interrupting these steps would ultimately prove fatal to the bacterial cell. The mechanisms of these ligases are well understood and the structures of all four of these ligases are now known. A detailed comparison of these four enzymes shows that considerable conformational changes are possible and that these changes, along with the recruitment of two different N-terminal binding domains, allows these enzymes to bind a substrate which at one end is identical and at the other has the growing polypeptide tail. Some insights into the structure-function relationships in these enzymes is presented.
Smith
Clyde A
CA
Stanford Synchrotron Radiation Laboratory, Menlo Park, CA 94025, USA. csmith@slac.stanford.edu
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001419:Bacteria / Q000166:cytology / Q000201:enzymology*; D002473:Cell Wall / Q000201:enzymology*; D008025:Ligases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000255:Adenosine Triphosphate; D008025:Ligases