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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI009152-20
Application #
3124512
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1975-01-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
20
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138