3SRC

Structure of Pseudomonas aeruginosa PvdQ bound to NS2028

3SRC の概要

• エントリーDOI: 10.2210/pdb3src/pdb
• 関連するPDBエントリー: 2WYB 2WYC 2WYD 2WYE 3L91 3L94 3SRA 3SRB
• 分子名称: Acyl-homoserine lactone acylase pvdQ, 1,2-ETHANEDIOL, 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one, ... (5 entities in total)
• 機能のキーワード: nrps tailoring, acylase, liganded, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Pseudomonas aeruginosa; 詳細
• 細胞内の位置: Periplasm (Probable): Q9I194 Q9I194
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79772.27

構造登録者

Gulick, A.M.,Drake, E.J. (登録日: 2011-07-07, 公開日: 2011-09-21, 最終更新日: 2024-10-30)

主引用文献

Drake, E.J.,Gulick, A.M.
Structural Characterization and High-Throughput Screening of Inhibitors of PvdQ, an NTN Hydrolase Involved in Pyoverdine Synthesis.
Acs Chem.Biol., 6:1277-1286, 2011

PubMed Abstract: The human pathogen Pseudomonas aeruginosa produces a variety of virulence factors including pyoverdine, a nonribosomally produced peptide siderophore. The maturation pathway of the pyoverdine peptide is complex and provides a unique target for inhibition. Within the pyoverdine biosynthetic cluster is a periplasmic hydrolase, PvdQ, that is required for pyoverdine production. However, the precise role of PvdQ in the maturation pathway has not been biochemically characterized. We demonstrate herein that the initial module of the nonribosomal peptide synthetase PvdL adds a myristate moiety to the pyoverdine precursor. We extracted this acylated precursor, called PVDIq, from a pvdQ mutant strain and show that the PvdQ enzyme removes the fatty acid catalyzing one of the final steps in pyoverdine maturation. Incubation of PVDIq with crystals of PvdQ allowed us to capture the acylated enzyme and confirm through structural studies the chemical composition of the incorporated acyl chain. Finally, because inhibition of siderophore synthesis has been identified as a potential antibiotic strategy, we developed a high-throughput screening assay and tested a small chemical library for compounds that inhibit PvdQ activity. Two compounds that block PvdQ have been identified, and their binding within the fatty acid binding pocket was structurally characterized.

PubMed: 21892836
DOI: 10.1021/cb2002973

実験手法

X-RAY DIFFRACTION (2 Å)