8DA2

Acinetobacter baumannii L,D-transpeptidase

8DA2 の概要

• エントリーDOI: 10.2210/pdb8da2/pdb
• 分子名称: L,D-transpeptidase family protein (2 entities in total)
• 機能のキーワード: cell wall, transpeptidase, peptidoglycan, transferase
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42314.62

構造登録者

Toth, M.,Stewart, N.K.,Smith, C.A.,Vakulenko, S.B. (登録日: 2022-06-12, 公開日: 2022-09-14, 最終更新日: 2024-05-22)

主引用文献

Toth, M.,Stewart, N.K.,Smith, C.A.,Lee, M.,Vakulenko, S.B.
The l,d-Transpeptidase Ldt Ab from Acinetobacter baumannii Is Poorly Inhibited by Carbapenems and Has a Unique Structural Architecture.
Acs Infect Dis., 8:1948-1961, 2022

PubMed Abstract: l,d-Transpeptidases (LDTs) are enzymes that catalyze reactions essential for biogenesis of the bacterial cell wall, including formation of 3-3 cross-linked peptidoglycan. Unlike the historically well-known bacterial transpeptidases, the penicillin-binding proteins (PBPs), LDTs are resistant to inhibition by the majority of β-lactam antibiotics, with the exception of carbapenems and penems, allowing bacteria to survive in the presence of these drugs. Here we report characterization of Ldt from the clinically important pathogen, . We show that survives inactivation of Ldt alone or in combination with PBP1b or PBP2, while simultaneous inactivation of Ldt and PBP1a is lethal. Minimal inhibitory concentrations (MICs) of all 13 β-lactam antibiotics tested decreased 2- to 8-fold for the Ldt deletion mutant, while further decreases were seen for both double mutants, with the largest, synergistic effect observed for the Ldt + PBP2 deletion mutant. Mass spectrometry experiments showed that Ldt forms complexes in vitro only with carbapenems. However, the acylation rate of these antibiotics is very slow, with the reaction taking longer than four hours to complete. Our X-ray crystallographic studies revealed that Ldt has a unique structural architecture and is the only known LDT to have two different peptidoglycan-binding domains.

PubMed: 35973205
DOI: 10.1021/acsinfecdis.2c00321

実験手法

X-RAY DIFFRACTION (2.6 Å)