5CHM

CRYSTAL STRUCTURE OF Fox-4 cephamycinase complexed with ceftazidime BATSI (LP06)

Summary for 5CHM

• Entry DOI: 10.2210/pdb5chm/pdb
• Related: 5CGS 5CGW 5CGX 5CHJ
• Descriptor: Beta-lactamase, PINACOL[[2-AMINO-ALPHA-(1-CARBOXY-1-METHYLETHOXYIMINO)-4-THIAZOLEACETYL]AMINO]METHANEBORONATE, ZINC ION, ... (6 entities in total)
• Functional Keywords: beta-lactamase, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 39547.00

Authors

Malashkevich, V.N.,Toro, R.,Lefurgy, S.,Almo, S.C. (deposition date: 2015-07-10, release date: 2016-08-03, Last modification date: 2024-10-23)

Primary citation

Lefurgy, S.T.,Caselli, E.,Taracila, M.A.,Malashkevich, V.N.,Biju, B.,Papp-Wallace, K.M.,Bonanno, J.B.,Prati, F.,Almo, S.C.,Bonomo, R.A.
Structures of FOX-4 Cephamycinase in Complex with Transition-State Analog Inhibitors.
Biomolecules, 10:-, 2020

PubMed Abstract: Boronic acid transition-state analog inhibitors (BATSIs) are partners with β-lactam antibiotics for the treatment of complex bacterial infections. Herein, microbiological, biochemical, and structural findings on four BATSIs with the FOX-4 cephamycinase, a class C β-lactamase that rapidly hydrolyzes cefoxitin, are revealed. FOX-4 is an extended-spectrum class C cephalosporinase that demonstrates conformational flexibility when complexed with certain ligands. Like other β-lactamases of this class, studies on FOX-4 reveal important insights into structure-activity relationships. We show that SM23, a BATSI, shows both remarkable flexibility and affinity, binding similarly to other β-lactamases, yet retaining an IC value < 0.1 μM. Our analyses open up new opportunities for the design of novel transition-state analogs of class C enzymes.

PubMed: 32349291
DOI: 10.3390/biom10050671

Experimental method

X-RAY DIFFRACTION (1.9 Å)