Wide-open conformation of UDP-MurNc-tripeptide ligase revealed by the substrate-free structure of MurE from Acinetobacter baumannii

FEBS Letters

article

Kyoung Ho Jung¹  Yeon-Gil Kim³  Chang Min Kim¹  Hyun Ji Ha¹  Chang Sup Lee⁴  Jun Hyuck Lee⁵  Hyun Ho Park¹ 

[1] Department of Global Innovative Drugs, Graduate School of Chung-Ang University;College of Pharmacy, Chung-Ang University;Pohang Accelerator Laboratory, Pohang University of Science and Technology;College of Pharmacy and Research Institute of Pharmaceutical Science, Gyeongsang National University;Unit of Research for Practical Application, Korea Polar Research Institute, Incheon;Department of Polar Sciences, University of Science and Technology, Incheon

关键词: Acinetobacter baumannii;    ATP-dependent ligase;    cell wall peptidoglycan biosynthesis;    crystal structure;    MurE;   

DOI  :  10.1002/1873-3468.14007

来源: John Wiley & Sons Ltd.

【 摘 要 】

MurE ligase catalyzes the attachment of meso -diaminopimelic acid to the UDP-MurNAc- l -Ala- d -Glu using ATP and producing UDP-MurNAc- l -Ala- d -Glu- meso -A 2 pm during bacterial cell wall biosynthesis. Owing to the critical role of this enzyme, MurE is considered an attractive target for antibacterial drugs. Despite extensive studies on MurE ligase, the structural dynamics of its conformational changes are still elusive. In this study, we present the substrate-free structure of MurE from Acinetobacter baumannii , which is an antibiotic-resistant superbacterium that has threatened global public health. The structure revealed that MurE has a wide-open conformation and undergoes wide-open, intermediately closed, and fully closed dynamic conformational transition. Unveiling structural dynamics of MurE will help to understand the working mechanism of this ligase and to design next-generation antibiotics targeting MurE.

【 授权许可】

Unknown