2Y2O

PENICILLIN-BINDING PROTEIN 1B (PBP-1B) IN COMPLEX WITH AN ALKYL BORONATE (EO9)

2Y2O の概要

• エントリーDOI: 10.2210/pdb2y2o/pdb
• 関連するPDBエントリー: 2UWX 2XD1 2XD5 2Y2G 2Y2H 2Y2I 2Y2J 2Y2K 2Y2L 2Y2M 2Y2N 2Y2P 2Y2Q
• 分子名称: PENICILLIN-BINDING PROTEIN 1B, [(1S)-1-[(2,6-difluorophenyl)carbonylamino]ethyl]-trihydroxy-boron, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: transferase, infection, cell wall, peptidoglycan, inhibitor
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54958.30

構造登録者

Contreras-Martel, C.,Amoroso, A.,Woon, E.C.,Zervosen, A.,Inglis, S.,Martins, A.,Verlaine, O.,Rydzik, A.,Job, V.,Luxen, A.,Joris, B.,Schofield, C.J.,Dessen, A. (登録日: 2010-12-15, 公開日: 2011-08-03, 最終更新日: 2024-10-23)

主引用文献

Contreras-Martel, C.,Amoroso, A.,Woon, E.C.,Zervosen, A.,Inglis, S.,Martins, A.,Verlaine, O.,Rydzik, A.,Job, V.,Luxen, A.,Joris, B.,Schofield, C.J.,Dessen, A.
Structure-Guided Design of Cell Wall Biosynthesis Inhibitors that Overcome Beta-Lactam Resistance in Staphylococcus Aureus (Mrsa).
Acs Chem.Biol., 6:943-, 2011

PubMed Abstract: β-Lactam antibiotics have long been a treatment of choice for bacterial infections since they bind irreversibly to Penicillin-Binding Proteins (PBPs), enzymes that are vital for cell wall biosynthesis. Many pathogens express drug-insensitive PBPs rendering β-lactams ineffective, revealing a need for new types of PBP inhibitors active against resistant strains. We have identified alkyl boronic acids that are active against pathogens including methicillin-resistant S. aureus (MRSA). The crystal structures of PBP1b complexed to 11 different alkyl boronates demonstrate that in vivo efficacy correlates with the mode of inhibitor side chain binding. Staphylococcal membrane analyses reveal that the most potent alkyl boronate targets PBP1, an autolysis system regulator, and PBP2a, a low β-lactam affinity enzyme. This work demonstrates the potential of boronate-based PBP inhibitors for circumventing β-lactam resistance and opens avenues for the development of novel antibiotics that target Gram-positive pathogens.

PubMed: 21732689
DOI: 10.1021/CB2001846

実験手法

X-RAY DIFFRACTION (1.88 Å)