5AH4
The sliding clamp of Mycobacterium smegmatis in complex with a natural product.
Summary for 5AH4
| Entry DOI | 10.2210/pdb5ah4/pdb |
| Related | 5AGU 5AGV 5AH2 |
| Related PRD ID | PRD_002466 |
| Descriptor | DNA POLYMERASE III SUBUNIT BETA, CYCLOHEXYL GRISELIMYCIN, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | transferase-antibiotic complex, dnan, dna polymerase, tuberculosis, transferase/antibiotic |
| Biological source | MYCOBACTERIUM SMEGMATIS More |
| Total number of polymer chains | 4 |
| Total formula weight | 85802.34 |
| Authors | Lukat, P.,Kling, A.,Heinz, D.W.,Mueller, R. (deposition date: 2015-02-04, release date: 2015-06-03, Last modification date: 2024-01-10) |
| Primary citation | Kling, A.,Lukat, P.,Almeida, D.V.,Bauer, A.,Fontaine, E.,Sordello, S.,Zaburannyi, N.,Herrmann, J.,Wenzel, S.C.,Konig, C.,Ammerman, N.C.,Barrio, M.B.,Borchers, K.,Bordon-Pallier, F.,Bronstrup, 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.,Muller, R. Antibiotics. Targeting Dnan for Tuberculosis Therapy Using Novel Griselimycins. Science, 348:1106-, 2015 Cited by 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: 26045430DOI: 10.1126/SCIENCE.AAA4690 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.313 Å) |
Structure validation
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