6UED

Apo Pseudomonas aeruginosa LpxD Structure

6UED の概要

• エントリーDOI: 10.2210/pdb6ued/pdb
• 分子名称: UDP-3-O-acylglucosamine N-acyltransferase, GLYCEROL, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: lpxd, apo, trimer, acyl transferase, transferase
• 由来する生物種: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38372.50

構造登録者

Chen, Y.,Kroeck, K.,Sacco, M. (登録日: 2019-09-20, 公開日: 2019-11-13, 最終更新日: 2024-03-13)

主引用文献

Kroeck, K.G.,Sacco, M.D.,Smith, E.W.,Zhang, X.,Shoun, D.,Akhtar, A.,Darch, S.E.,Cohen, F.,Andrews, L.D.,Knox, J.E.,Chen, Y.
Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography.
Sci Rep, 9:15450-15450, 2019

PubMed Abstract: The lipid A biosynthesis pathway is essential in Pseudomonas aeruginosa. LpxA and LpxD are the first and third enzymes in this pathway respectively, and are regarded as promising antibiotic targets. The unique structural similarities between these two enzymes make them suitable targets for dual-binding inhibitors, a characteristic that would decrease the likelihood of mutational resistance and increase cell-based activity. We report the discovery of multiple small molecule ligands that bind to P. aeruginosa LpxA and LpxD, including dual-binding ligands. Binding poses were determined for select compounds by X-ray crystallography. The new structures reveal a previously uncharacterized magnesium ion residing at the core of the LpxD trimer. In addition, ligand binding in the LpxD active site resulted in conformational changes in the distal C-terminal helix-bundle, which forms extensive contacts with acyl carrier protein (ACP) during catalysis. These ligand-dependent conformational changes suggest a potential allosteric influence of reaction intermediates on ACP binding, and vice versa. Taken together, the novel small molecule ligands and their crystal structures provide new chemical scaffolds for ligand discovery targeting lipid A biosynthesis, while revealing structural features of interest for future investigation of LpxD function.

PubMed: 31664082
DOI: 10.1038/s41598-019-51844-z

実験手法

X-RAY DIFFRACTION (1.55 Å)