Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA.
Department of Chemistry and Biochemistry, Northern Kentucky University, Highland Heights, Kentucky, 41099, USA.
J Biol Inorg Chem. 2022 Sep;27(6):541-551. doi: 10.1007/s00775-022-01941-8. Epub 2022 May 5.
Pseudomonas aeruginosa is an increasingly antibiotic-resistant pathogen that causes severe lung infections, burn wound infections, and diabetic foot infections. P. aeruginosa produces the siderophore pyochelin through the use of a non-ribosomal peptide synthetase (NRPS) biosynthetic pathway. Targeting members of siderophore NRPS proteins is one avenue currently under investigation for the development of new antibiotics against antibiotic-resistant organisms. Here, the crystal structure of the pyochelin adenylation domain PchD is reported. The structure was solved to 2.11 Å when co-crystallized with the adenylation inhibitor 5'-O-(N-salicylsulfamoyl)adenosine (salicyl-AMS) and to 1.69 Å with a modified version of salicyl-AMS designed to target an active site cysteine (4-cyano-salicyl-AMS). In the structures, PchD adopts the adenylation conformation, similar to that reported for AB3403 from Acinetobacter baumannii.
铜绿假单胞菌是一种对抗生素耐药性日益增强的病原体，可导致严重的肺部感染、烧伤创面感染和糖尿病足感染。铜绿假单胞菌通过非核糖体肽合成酶（NRPS）生物合成途径产生铁载体焦脱镁叶绿酸。针对铁载体 NRPS 蛋白成员是目前正在研究的开发针对抗药性生物体的新抗生素的一种途径。本文报道了焦脱镁叶绿酸腺苷酰化酶 PchD 的晶体结构。当与腺苷酸化抑制剂 5'-O-（N-水杨基磺酰胺基）腺苷（水杨基-AMS）共结晶时，该结构解析到 2.11Å，与设计用于靶向活性位点半胱氨酸（4-氰基水杨基-AMS）的水杨基-AMS 的修饰版本一起解析到 1.69Å。在这些结构中，PchD 采用腺苷酸化构象，类似于鲍曼不动杆菌 AB3403 报道的构象。
