5ZQC

Crystal Structure of Penicillin-Binding Protein D2 from Listeria monocytogenes in the Ampicillin bound form

Summary for 5ZQC

• Entry DOI: 10.2210/pdb5zqc/pdb
• Descriptor: Lmo2812 protein, (2R,4S)-2-[(1R)-1-{[(2R)-2-amino-2-phenylacetyl]amino}-2-oxoethyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, GLYCEROL, ... (4 entities in total)
• Functional Keywords: listeria monocytogenes, hypothetical, penicillin-binding protein, lmpbpd2, lmo2812, antibiotic
• Biological source: Listeria monocytogenes EGD-e
• Total number of polymer chains: 4
• Total formula weight: 122140.48

Authors

Jeong, J.H.,Kim, Y.G. (deposition date: 2018-04-18, release date: 2018-08-01, Last modification date: 2024-11-06)

Primary citation

Jeong, J.H.,Cha, H.J.,Kim, Y.G.
Crystal Structures of Penicillin-Binding Protein D2 from Listeria monocytogenes and Structural Basis for Antibiotic Specificity
Antimicrob. Agents Chemother., 62:-, 2018

PubMed Abstract: β-Lactam antibiotics that inhibit penicillin-binding proteins (PBPs) have been widely used in the treatment of bacterial infections. However, the molecular basis underlying the different inhibitory potencies of β-lactams against specific PBPs is not fully understood. Here, we present the crystal structures of penicillin-binding protein D2 (PBPD2) from , a Gram-positive foodborne bacterial pathogen that causes listeriosis in humans. The acylated structures in complex with four antibiotics (penicillin G, ampicillin, cefotaxime, and cefuroxime) revealed that the β-lactam core structures were recognized by a common set of residues; however, the R1 side chains of each antibiotic participate in different interactions with PBPD2. In addition, the structural complementarities between the side chains of β-lactams and the enzyme were found to be highly correlated with the relative reactivities of penam or cephem antibiotics against PBPD2. Our study provides the structural basis for the inhibition of PBPD2 by clinically important β-lactam antibiotics that are commonly used in listeriosis treatment. Our findings imply that the modification of β-lactam side chains based on structural complementarity could be useful for the development of potent inhibitors against β-lactam-resistant PBPs.

PubMed: 30082290
DOI: 10.1128/AAC.00796-18

Experimental method

X-RAY DIFFRACTION (1.702 Å)