1LLB

Crystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With ATMO-penicillin

Summary for 1LLB

• Entry DOI: 10.2210/pdb1llb/pdb
• Related: 1FCN 1FR6 1IEL 1IEM 1KE4 1KVM 1LL9
• Descriptor: beta-lactamase, 2-{1-[2-(2-AMINO-THIAZOL-4-YL)-2-METHOXYIMINO-ACETYLAMINO]-2-OXO-ETHYL}-5,5-DIMETHYL-THIAZOLIDINE-4-CARBOXYLIC ACID (3 entities in total)
• Functional Keywords: cephalosporinase, beta-lactamase, serine, hydrolase
• Biological source: Escherichia coli
• Cellular location: Periplasm: P00811
• Total number of polymer chains: 2
• Total formula weight: 79577.30

Authors

Trehan, I.,Morandi, F.,Blaszczak, L.C.,Shoichet, B.K. (deposition date: 2002-04-26, release date: 2002-10-02, Last modification date: 2024-11-06)

Primary citation

Trehan, I.,Morandi, F.,Blaszczak, L.C.,Shoichet, B.K.
Using steric hindrance to design new inhibitors of class C beta-lactamases.
Chem.Biol., 9:971-980, 2002

PubMed Abstract: 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.

PubMed: 12323371
DOI: 10.1016/S1074-5521(02)00211-9

Experimental method

X-RAY DIFFRACTION (1.72 Å)