2Z2L: Penicillin-binding Protein 2x (pbp2x) From Streptococcus Pneumoniae

Citation:
Abstract
Cefditoren is the active form of cefditoren pivoxil, an oral cephalosporin antibiotic used for the treatment of respiratory tract infections and otitis media caused by bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, and methicillin-susceptible strains of Staphylococcus aureus. Beta-lactam antibiotics, including cefditoren, target penicillin-binding proteins (PBPs), which are membrane-associated enzymes that play essential roles in the peptidoglycan biosynthetic process. To envision the binding of cefditoren to PBPs, we determined the crystal structure of a trypsin-digested form of PBP 2X from S. pneumoniae strain R6 complexed with cefditoren. There are two PBP 2X molecules (designated molecules 1 and 2) per asymmetric unit. The structure reveals that the orientation of Trp374 in each molecule changes in a different way upon the formation of the complex, but each forms a hydrophobic pocket. The methylthiazole group of the C-3 side chain of cefditoren fits into this binding pocket, which consists of residues His394, Trp374, and Thr526 in molecule 1 and residues His394, Asp375, and Thr526 in molecule 2. The formation of the complex is also accompanied by an induced-fit conformational change of the enzyme in the pocket to which the C-7 side chain of cefditoren binds. These features likely play a role in the high level of activity of cefditoren against S. pneumoniae.
PDB ID: 2Z2LDownload
MMDB ID: 59960
PDB Deposition Date: 2007/5/23
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.85  Å
Source Organism:
Similar Structures:
Biological Unit for 2Z2L: trimeric; determined by author
Molecular Components in 2Z2L
Label Count Molecule
Proteins (3 molecules)
1
Penicillin-binding Protein 2X(Gene symbol: pbpX)
Molecule annotation
1
Penicillin-binding Protein 2X(Gene symbol: pbpX)
Molecule annotation
1
Penicillin-binding Protein 2X(Gene symbol: pbpX)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.