1LLB: Crystal Structure Of Ampc Beta-Lactamase From E. Coli In Complex With Atmo-Penicillin

beta-lactamases confer resistance to beta-lactam antibiotics such as penicillins and cephalosporins. However, beta-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of beta-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R(1) side chain of beta-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective beta-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.
PDB ID: 1LLBDownload
MMDB ID: 20661
PDB Deposition Date: 2002/4/26
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.72  Å
Source Organism:
Similar Structures:
Biological Unit for 1LLB: monomeric; determined by author
Molecular Components in 1LLB
Label Count Molecule
Protein (1 molecule)
Beta-lactamase(Gene symbol: ampC)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB