2V2F

Crystal structure of PBP1a from drug-resistant strain 5204 from Streptococcus pneumoniae

2V2F の概要

• エントリーDOI: 10.2210/pdb2v2f/pdb
• 分子名称: PENICILLIN BINDING PROTEIN 1A, BARIUM ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: transpeptidase activity, peptidoglycan synthesis, transferase, hydrolase
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46404.52

構造登録者

Job, V.,Carapito, R.,Vernet, T.,Dideberg, O.,Dessen, A.,Zapun, A. (登録日: 2007-06-05, 公開日: 2007-12-25, 最終更新日: 2023-12-13)

主引用文献

Job, V.,Carapito, R.,Vernet, T.,Dessen, A.,Zapun, A.
Common Alterations in Pbp1A from Resistant Streptococcus Pneumoniae Decrease its Reactivity Toward {Beta}-Lactams: Structural Insights.
J.Biol.Chem., 283:4886-, 2008

PubMed Abstract: The development of high level beta-lactam resistance in the pneumococcus requires the expression of an altered form of PBP1a, in addition to modified forms of PBP2b and PBP2x, which are necessary for the appearance of low levels of resistance. Here, we present the crystal structure of a soluble form of PBP1a from the highly resistant Streptococcus pneumoniae strain 5204 (minimal inhibitory concentration of cefotaxime is 12 mg.liter(-1)). Mutations T371A, which is adjacent to the catalytic nucleophile Ser370, and TSQF(574-577)NTGY, which lie in a loop bordering the active site cleft, were investigated by site-directed mutagenesis. The consequences of these substitutions on reaction kinetics with beta-lactams were probed in vitro, and their effect on resistance was measured in vivo. The results are interpreted in the framework of the crystal structure, which displays a narrower, discontinuous active site cavity, compared with that of PBP1a from the beta-lactam susceptible strain R6, as well as a reorientation of the catalytic Ser370.

PubMed: 18055459
DOI: 10.1074/JBC.M706181200

実験手法

X-RAY DIFFRACTION (1.9 Å)