3ZG7

Crystal Structure of Penicillin-Binding Protein 4 from Listeria monocytogenes in the apo form

Summary for 3ZG7

• Entry DOI: 10.2210/pdb3zg7/pdb
• Related: 3ZG8 3ZG9 3ZGA
• Descriptor: PENICILLIN-BINDING PROTEIN 4, L(+)-TARTARIC ACID, GLYCEROL, ... (5 entities in total)
• Functional Keywords: penicillin-binding protein
• Biological source: LISTERIA MONOCYTOGENES; More
• Total number of polymer chains: 2
• Total formula weight: 64188.50

Authors

Jeong, J.H.,Kim, Y.G. (deposition date: 2012-12-17, release date: 2013-05-29, Last modification date: 2013-07-31)

Primary citation

Jeong, J.,Kim, Y.,Rojviriya, C.,Ha, S.,Kang, B.S.,Kim, Y.
Crystal Structures of Bifunctional Penicillin-Binding Protein 4 from Listeria Monocytogenes.
Antimicrob.Agents Chemother., 57:3507-, 2013

PubMed Abstract: Penicillin-binding proteins (PBPs), which catalyze the biosynthesis of the peptidoglycan chain of the bacterial cell wall, are the major molecular target of bacterial antibiotics. Here, we present the crystal structures of the bifunctional peptidoglycan glycosyltransferase (GT)/transpeptidase (TP) PBP4 from Listeria monocytogenes in the apo-form and covalently linked to two β-lactam antibiotics, ampicillin and carbenicillin. The orientation of the TP domain with respect to the GT domain is distinct from that observed in the previously reported structures of bifunctional PBPs, suggesting interdomain flexibility. In this structure, the active site of the GT domain is occluded by the close apposition of the linker domain, which supports the hypothesis that interdomain flexibility is related to the regulation of GT activity. The acylated structures reveal the mode of action of β-lactam antibiotics toward the class A PBP4 from the human pathogen L. monocytogenes. Ampicillin and carbenicillin can access the active site and be acylated without requiring a structural rearrangement. In addition, the active site of the TP domain in the apo-form is occupied by the tartrate molecule via extensive hydrogen bond interactions with the catalytically important residues; thus, derivatives of the tartrate molecule may be useful in the search for new antibiotics to inhibit PBPs.

PubMed: 23669378
DOI: 10.1128/AAC.00144-13

Experimental method

X-RAY DIFFRACTION (1.991 Å)