Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors
10.16438/j.0513-4870.2023-0903
- VernacularTitle:抗革兰阴性菌新靶标: 脂多糖转运蛋白LptDE及其抑制剂研究进展
- Author:
Yue LI
1
;
Guo-qing LI
2
;
Yuan-yuan TIAN
3
;
Cong-ran LI
2
;
Xin-yi YANG
2
;
Kai-hu YAO
1
;
Xue-fu YOU
2
Author Information
1. National Center for Children's Health/Beijing Children's Hospital, Capital Medical University/Beijing Pediatric Research Institute/National Clinical Research Center for Respiratory Diseases/Key Laboratory of Major Diseases in Children, Ministry of Education/Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing 100045, China
2. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
3. Department of Dermatology, National Center for Children's Health/Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
- Publication Type:Research Article
- Keywords:
Gram-negative bacteria;
lipopolysaccharide outer membrane;
lipopolysaccharide transport protein complex DE;
new antibacterial drug target;
novel peptidomimetic compound
- From:
Acta Pharmaceutica Sinica
2024;59(2):279-288
- CountryChina
- Language:Chinese
-
Abstract:
The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.
