8IBP

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

Summary for 8IBP

• Entry DOI: 10.2210/pdb8ibp/pdb
• Related: 8IBO
• Descriptor: Negative regulator of genetic competence ClpC/mecB, Lassomycin, ACETATE ION, ... (4 entities in total)
• Functional Keywords: chaperone
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 2
• Total formula weight: 17732.42

Authors

Jagdev, M.K.,Vasudevan, D. (deposition date: 2023-02-10, release date: 2023-09-20, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.45 Å)