8IBP

Crystal structure of Mycobacterium tuberculosis R21K ClpC1 N-terminal domain in complex with Lassomycin

8IBP の概要

• エントリーDOI: 10.2210/pdb8ibp/pdb
• 関連するPDBエントリー: 8IBO
• 分子名称: Negative regulator of genetic competence ClpC/mecB, Lassomycin, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: chaperone
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 17732.42

構造登録者

Jagdev, M.K.,Vasudevan, D. (登録日: 2023-02-10, 公開日: 2023-09-20, 最終更新日: 2024-05-08)

主引用文献

Jagdev, M.K.,Tompa, D.R.,Ling, L.L.,Peoples, A.J.,Dandapat, J.,Mohapatra, C.,Lewis, K.,Vasudevan, D.
Crystal structure of the N-terminal domain of MtClpC1 in complex with the anti-mycobacterial natural peptide Lassomycin.
Int.J.Biol.Macromol., 253:126771-126771, 2023

PubMed Abstract: Antibiotics form our frontline therapy against disease-causing bacteria. Unfortunately, antibiotic resistance is becoming more common, threatening a future where these medications can no longer cure infections. Furthermore, the emergence of multidrug-resistant (MDR), totally drug-resistant (TDR), and extensively drug-resistant (XDR) tuberculosis has increased the urgency of discovering new therapeutic leads with unique modes of action. Some natural peptides derived from actinomycetes, such as Cyclomarin A, Lassomycin, Rufomycin I, and Ecumicin, have potent and specific bactericidal activity against Mycobacterium tuberculosis, with the specificity owing to the fact that these peptides target the ClpC1 ATPase, an essential enzyme in mycobacteria, and inhibit/activate the proteolytic activity of the ClpC1/P1/P2 complex that participates in protein homeostasis. Here, we report the high-resolution crystal structure of the N-terminal domain of ClpC1 (ClpC1 NTD) in complex with Lassomycin, showing the specific binding mode of Lassomycin. In addition, the work also compares the Lassomycin complex structure with the previously known structures of ClpC1 NTD in complex with other natural peptides such as Cyclomarin A, Rufomycin I, and Ecumicin.

PubMed: 37683752
DOI: 10.1016/j.ijbiomac.2023.126771

実験手法

X-RAY DIFFRACTION (1.45 Å)