The general objective of the present work is to study in as much detail as possible the mechanism of inhibition of bacterial growth by penicillins, cephalosporins and other Beta-lactam antibodies. During the present phase the main effort will be: 1) to elucidate the sequences of the active site peptides of the high molecular weight penicillin binding proteins of Escherichia coli (PBPs 1a, 1b, 2 and 3) in order to localize the active site peptides within the primary amino acid sequences derived from DNA clones, 2) similarly, to identify and localize the hydrophobic membrane-spanning peptide(s) of these penicillin-binding proteins as well as that of PBP 5 and 3) to crystallize one or more of these penicillin-binding proteins, either in the presence of the detergent or as a catalytically active water soluble proteolytic degradation product, in order to determine the x-ray crystallographic structure. These data should provide much useful information for the improved rational design of penicillins, cephalosporins and related Beta-lactam antibiotics.
| Nicholas, R A; Ishino, F; Park, W et al. (1985) Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 5 from the dacA mutant strain of Escherichia coli (TMRL 1222). J Biol Chem 260:6394-7 |
| Nicholas, R A; Suzuki, H; Hirota, Y et al. (1985) Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 1b of Escherichia coli. Biochemistry 24:3448-53 |
| Nicholas, R A; Strominger, J L; Suzuki, H et al. (1985) Identification of the active site in penicillin-binding protein 3 of Escherichia coli. J Bacteriol 164:456-60 |
