5AH2

The sliding clamp of Mycobacterium smegmatis in complex with a natural product.

5AH2 の概要

• エントリーDOI: 10.2210/pdb5ah2/pdb
• 関連するPDBエントリー: 5AGU 5AGV 5AH4
• 関連するBIRD辞書のPRD_ID: PRD_002311
• 分子名称: DNA POLYMERASE III SUBUNIT BETA, GRISELIMYCIN, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: transferase-antibiotic complex, dnan, dna polymerase, tuberculosis, transferase/antibiotic
• 由来する生物種: MYCOBACTERIUM SMEGMATIS; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 171276.10

構造登録者

Lukat, P.,Kling, A.,Heinz, D.W.,Mueller, R. (登録日: 2015-02-04, 公開日: 2015-06-03, 最終更新日: 2024-01-10)

主引用文献

Kling, A.,Lukat, P.,Almeida, D.V.,Bauer, A.,Fontaine, E.,Sordello, S.,Zaburannyi, N.,Herrmann, J.,Wenzel, S.C.,Koenig, C.,Ammermann, N.C.,Barrio, M.B.,Borchers, K.,Bordon-Pallier, F.,Broenstrup, M.,Courtemanche, G.,Gerlitz, M.,Geslin, M.,Hammann, P.,Heinz, D.W.,Hoffmann, H.,Klieber, S.,Kohlmann, M.,Kurz, M.,Lair, C.,Matter, H.,Nuermberger, E.,Tyagi, S.,Fraisse, L.,Grosset, J.H.,Lagrange, S.,Mueller, R.
Antibiotics. Targeting Dnan for Tuberculosis Therapy Using Novel Griselimycins.
Science, 348:1106-, 2015

PubMed Abstract: The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification.

PubMed: 26045430
DOI: 10.1126/SCIENCE.AAA4690

実験手法

X-RAY DIFFRACTION (2.129 Å)