2MC0
Structural Basis of a Thiopeptide Antibiotic Multidrug Resistance System from Streptomyces lividans:Nosiheptide in Complex with TipAS
Summary for 2MC0
| Entry DOI | 10.2210/pdb2mc0/pdb |
| Related | 1NY9 2mbz |
| NMR Information | BMRB: 19422 |
| Related PRD ID | PRD_001172 |
| Descriptor | HTH-type transcriptional activator TipA, nosiheptide, 4-(hydroxymethyl)-3-methyl-1H-indole-2-carboxylic acid (3 entities in total) |
| Functional Keywords | bacterial protein, streptomyces lividans, transcriptional activation, tipas-nosiheptide complex, transcriptional activator-antibiotic complex, protein/thiopeptide, multidrug recognition, transcription activator-antibiotic complex, transcription activator/antibiotic |
| Biological source | Streptomyces lividans More |
| Total number of polymer chains | 2 |
| Total formula weight | 17986.64 |
| Authors | Habazettl, J.,Allan, M.G.,Jensen, P.,Sass, H.,Grzesiek, S. (deposition date: 2013-08-12, release date: 2014-12-10, Last modification date: 2023-11-15) |
| Primary citation | Habazettl, J.,Allan, M.,Jensen, P.R.,Sass, H.J.,Thompson, C.J.,Grzesiek, S. Structural basis and dynamics of multidrug recognition in a minimal bacterial multidrug resistance system Proc.Natl.Acad.Sci.USA, 111:E5498-E5507, 2014 Cited by PubMed Abstract: TipA is a transcriptional regulator found in diverse bacteria. It constitutes a minimal autoregulated multidrug resistance system against numerous thiopeptide antibiotics. Here we report the structures of its drug-binding domain TipAS in complexes with promothiocin A and nosiheptide, and a model of the thiostrepton complex. Drug binding induces a large transition from a partially unfolded to a globin-like structure. The structures rationalize the mechanism of promiscuous, yet specific, drug recognition: (i) a four-ring motif present in all known TipA-inducing antibiotics is recognized specifically by conserved TipAS amino acids; and (ii) the variable part of the antibiotic is accommodated within a flexible cleft that rigidifies upon drug binding. Remarkably, the identified four-ring motif is also the major interacting part of the antibiotic with the ribosome. Hence the TipA multidrug resistance mechanism is directed against the same chemical motif that inhibits protein synthesis. The observed identity of chemical motifs responsible for antibiotic function and resistance may be a general principle and could help to better define new leads for antibiotics. PubMed: 25489067DOI: 10.1073/pnas.1412070111 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
