A bifunctional monocyclic beta-lactam cross-links across the active site of beta-lactamase.
A 4-alkoxy-2-azetidinone behaves as a bifunctional active site-directed inhibitor of the class A beta-lactamase from Bacillus cereus 569/H. It cross-links SER 70 and LYS 234 as it binds in a approximately 1:1 ratio. The cross-linked enzyme is irreversibly inhibited while the secondary structure is partially stabilized under conditions when the native enzyme is otherwise converted to a form with no detectable secondary structure by circular dichroism.
Ahluwalia
R
R
Department of Chemistry, University of Cincinnati, OH 45221-0172.
Day
R A
RA
Nauss
J
J
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D001409:Bacillus cereus / Q000201:enzymology; D001665:Binding Sites; D002942:Circular Dichroism; D003432:Cross-Linking Reagents; D008239:Lysine; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D017433:Protein Structure, Secondary; D012694:Serine; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry*
C091512:1-(4-methoxyphenyl)-3-acetamido-4-methoxyazetidin-2-one; D000081:Acetamides; D001384:Azetidines; D003432:Cross-Linking Reagents; D010446:Peptide Fragments; D065093:beta-Lactamase Inhibitors; D012694:Serine; D001618:beta-Lactamases; D008239:Lysine