2ZC6

Penicillin-binding protein 1A (PBP 1A) acyl-enzyme complex (tebipenem) from Streptococcus pneumoniae

2ZC6 の概要

• エントリーDOI: 10.2210/pdb2zc6/pdb
• 関連するPDBエントリー: 2ZC3 2ZC4 2ZC5
• 分子名称: Penicillin-binding protein 1A, ZINC ION, (4R,5S)-3-(1-(4,5-dihydrothiazol-2-yl)azetidin-3-ylthio)-5-((2S,3R)-3-hydroxy-1-oxobutan-2-yl)-4-methyl-4,5- dihydro-1H-pyrrole-2-carboxylic acid, ... (5 entities in total)
• 機能のキーワード: peptidoglycan synthesis, cell wall, penicillin-binding, antibiotics, tebipenem, antibiotic resistance, cell shape, cell wall biogenesis/degradation, multifunctional enzyme, secreted, biosynthetic protein
• 由来する生物種: Streptococcus pneumoniae; 詳細
• 細胞内の位置: Secreted: Q8DR59
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93706.05

構造登録者

Yamada, M.,Watanabe, T.,Takeuchi, Y. (登録日: 2007-11-02, 公開日: 2008-04-08, 最終更新日: 2024-10-23)

主引用文献

Yamada, M.,Watanabe, T.,Baba, N.,Takeuchi, Y.,Ohsawa, F.,Gomi, S.
Crystal Structures of Biapenem and Tebipenem Complexed with Penicillin-Binding Proteins 2X and 1A from Streptococcus pneumoniae
Antimicrob.Agents Chemother., 52:2053-2060, 2008

PubMed Abstract: Biapenem is a parenteral carbapenem antibiotic that exhibits wide-ranging antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Tebipenem is the active form of tebipenem pivoxil, a novel oral carbapenem antibiotic that has a high level of bioavailability in humans, in addition to the above-mentioned features. beta-lactam antibiotics, including carbapenems, target penicillin-binding proteins (PBPs), which are membrane-associated enzymes that play essential roles in peptidoglycan biosynthesis. To envisage the binding of carbapenems to PBPs, we determined the crystal structures of the trypsin-digested forms of both PBP 2X and PBP 1A from Streptococcus pneumoniae strain R6, each complexed with biapenem or tebipenem. The structures of the complexes revealed that the carbapenem C-2 side chains form hydrophobic interactions with Trp374 and Thr526 of PBP 2X and with Trp411 and Thr543 of PBP 1A. The Trp and Thr residues are conserved in PBP 2B. These results suggest that interactions between the C-2 side chains of carbapenems and the conserved Trp and Thr residues in PBPs play important roles in the binding of carbapenems to PBPs.

PubMed: 18391040
DOI: 10.1128/AAC.01456-07

実験手法

X-RAY DIFFRACTION (2.7 Å)