3OC2

Crystal structure of penicillin-binding protein 3 from Pseudomonas aeruginosa

3OC2 の概要

• エントリーDOI: 10.2210/pdb3oc2/pdb
• 分子名称: Penicillin-binding protein 3, CHLORIDE ION (3 entities in total)
• 機能のキーワード: penicillin-binding proteins, pseudomonas aeruginosa, structural genomics, oxford protein production facility, oppf, transpeptidase, cell wall biosynthesis, out periplasmic membrane, penicillin-binding protein
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61258.95

構造登録者

Sainsbury, S.,Bird, L.,Stuart, D.I.,Owens, R.J.,Ren, J.,Oxford Protein Production Facility (OPPF) (登録日: 2010-08-09, 公開日: 2010-11-10, 最終更新日: 2024-03-20)

主引用文献

Sainsbury, S.,Bird, L.,Rao, V.,Shepherd, S.M.,Stuart, D.I.,Hunter, W.N.,Owens, R.J.,Ren, J.
Crystal structures of penicillin-binding protein 3 from Pseudomonas aeruginosa: comparison of native and antibiotic-bound forms
J.Mol.Biol., 405:173-184, 2011

PubMed 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.

PubMed: 20974151
DOI: 10.1016/j.jmb.2010.10.024

実験手法

X-RAY DIFFRACTION (1.968 Å)