PDBsum entry 3ocn

Penicillin-binding protein/antibiotic

PDB id: 3ocn

Contents

Protein chain

503 a.a. *

Ligands

CTJ

Waters ×38

* Residue conservation analysis

PDB id:

3ocn

Name:

Penicillin-binding protein/antibiotic

Title:

Crystal structure of penicillin-binding protein 3 from pseudomonas aeruginosa in complex with ceftazidime

Structure:

Penicillin-binding protein 3. Chain: a. Fragment: residues in unp 35-579. Engineered: yes

Source:

Pseudomonas aeruginosa. Organism_taxid: 287. Strain: pao1. Gene: pa4418. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.61Å R-factor: 0.209 R-free: 0.263

Authors:

S.Sainsbury,L.Bird,D.I.Stuart,R.J.Owens,J.Ren,Oxford Protein Production Facility (Oppf)

Key ref:

S.Sainsbury et al. (2011). Crystal structures of penicillin-binding protein 3 from Pseudomonas aeruginosa: comparison of native and antibiotic-bound forms. J Mol Biol, 405, 173-184. PubMed id: 20974151

Date:

10-Aug-10 Release date: 10-Nov-10

Protein chain

Q51504  (Q51504_PSEAI) -  Peptidoglycan D,D-transpeptidase FtsI from Pseudomonas aeruginosa

Seq: 579 a.a.

Struc: 503 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.16.4 - serine-type D-Ala-D-Ala carboxypeptidase.
• Reaction: D-alanyl-D-alanine + H₂O = 2 D-alanine

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

J Mol Biol 405:173-184 (2011)

PubMed id: 20974151

Crystal structures of penicillin-binding protein 3 from Pseudomonas aeruginosa: comparison of native and antibiotic-bound forms.

S.Sainsbury, L.Bird, V.Rao, S.M.Shepherd, D.I.Stuart, W.N.Hunter, R.J.Owens, J.Ren.

ABSTRACT

We report the first crystal structures of a penicillin-binding protein (PBP), PBP3, from Pseudomonas aeruginosa in native form and covalently linked to two important β-lactam antibiotics, carbenicillin and ceftazidime. Overall, the structures of apo and acyl complexes are very similar; however, variations in the orientation of the amino-terminal membrane-proximal domain relative to that of the carboxy-terminal transpeptidase domain indicate interdomain flexibility. Binding of either carbenicillin or ceftazidime to purified PBP3 increases the thermostability of the enzyme significantly and is associated with local conformational changes, which lead to a narrowing of the substrate-binding cleft. The orientations of the two β-lactams in the active site and the key interactions formed between the ligands and PBP3 are similar despite differences in the two drugs, indicating a degree of flexibility in the binding site. The conserved binding mode of β-lactam-based inhibitors appears to extend to other PBPs, as suggested by a comparison of the PBP3/ceftazidime complex and the Escherichia coli PBP1b/ceftoxamine complex. Since P. aeruginosa is an important human pathogen, the structural data reveal the mode of action of the frontline antibiotic ceftazidime at the molecular level. Improved drugs to combat infections by P. aeruginosa and related Gram-negative bacteria are sought and our study provides templates to assist that process and allows us to discuss new ways of inhibiting PBPs.