3Q82

Meropenem acylated BlaR1 sensor domain from Staphylococcus aureus

3Q82 の概要

• エントリーDOI: 10.2210/pdb3q82/pdb
• 関連するPDBエントリー: 1XA1 3Q7V 3Q7Z 3Q81
• 分子名称: Beta-lactamase regulatory protein BlaR1, (4R,5S)-3-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-5-[(2S,3R)-3-hydroxy-1-oxobutan-2-yl]-4-methyl-4,5-d ihydro-1H-pyrrole-2-carboxylic acid, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: antibiotic-binding, mrsa, antibiotic-binding-antibiotic complex, hydrolase regulator-antibiotic complex, hydrolase regulator/antibiotic
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60401.93

構造登録者

Borbulevych, O.Y.,Mobashery, S.,Baker, B.M. (登録日: 2011-01-05, 公開日: 2011-07-20, 最終更新日: 2024-10-16)

主引用文献

Borbulevych, O.,Kumarasiri, M.,Wilson, B.,Llarrull, L.I.,Lee, M.,Hesek, D.,Shi, Q.,Peng, J.,Baker, B.M.,Mobashery, S.
Lysine Nzeta-decarboxylation switch and activation of the beta-lactam sensor domain of BlaR1 protein of methicillin-resistant Staphylococcus aureus.
J.Biol.Chem., 286:31466-31472, 2011

PubMed Abstract: The integral membrane protein BlaR1 of methicillin-resistant Staphylococcus aureus senses the presence of β-lactam antibiotics in the milieu and transduces the information to the cytoplasm, where the biochemical events that unleash induction of antibiotic resistance mechanisms take place. We report herein by two-dimensional and three-dimensional NMR experiments of the sensor domain of BlaR1 in solution and by determination of an x-ray structure for the apo protein that Lys-392 of the antibiotic-binding site is posttranslationally modified by N(ζ)-carboxylation. Additional crystallographic and NMR data reveal that on acylation of Ser-389 by antibiotics, Lys-392 experiences N(ζ)-decarboxylation. This unique process, termed the lysine N(ζ)-decarboxylation switch, arrests the sensor domain in the activated ("on") state, necessary for signal transduction and all the subsequent biochemical processes. We present structural information on how this receptor activation process takes place, imparting longevity to the antibiotic-receptor complex that is needed for the induction of the antibiotic-resistant phenotype in methicillin-resistant S. aureus.

PubMed: 21775440
DOI: 10.1074/jbc.M111.252189

実験手法

X-RAY DIFFRACTION (2.1 Å)