6VJS
Escherichia coli RNA polymerase and ureidothiophene-2-carboxylic acid complex
Summary for 6VJS
| Entry DOI | 10.2210/pdb6vjs/pdb |
| Descriptor | DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (8 entities in total) |
| Functional Keywords | rna polymerase transcription, transcription |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 12 |
| Total formula weight | 920596.41 |
| Authors | Murakami, K.S.,Molodtsov, V. (deposition date: 2020-01-17, release date: 2020-10-07, Last modification date: 2023-10-11) |
| Primary citation | Haupenthal, J.,Kautz, Y.,Elgaher, W.A.M.,Patzold, L.,Rohrig, T.,Laschke, M.W.,Tschernig, T.,Hirsch, A.K.H.,Molodtsov, V.,Murakami, K.S.,Hartmann, R.W.,Bischoff, M. Evaluation of Bacterial RNA Polymerase Inhibitors in a Staphylococcus aureus -Based Wound Infection Model in SKH1 Mice. Acs Infect Dis., 6:2573-2581, 2020 Cited by PubMed Abstract: Chronic wounds infected with pathogens such as represent a worldwide health concern, especially in patients with a compromised immune system. As antimicrobial resistance has become an immense global problem, novel antibiotics are urgently needed. One strategy to overcome this threatening situation is the search for drugs targeting novel binding sites on essential and validated enzymes such as the bacterial RNA polymerase (RNAP). In this work, we describe the establishment of an wound infection model based on the pathogen and hairless Crl:SKH1-Hrhr (SKH1) mice. The model proved to be a valuable preclinical tool to study selected RNAP inhibitors after topical application. While rifampicin showed a reduction in the loss of body weight induced by the bacteria, an acceleration of wound healing kinetics, and a reduced number of colony forming units in the wound, the ureidothiophene-2-carboxylic acid was inactive under conditions, probably due to strong plasma protein binding. The cocrystal structure of compound with RNAP, that we hereby also present, will be of great value for applying appropriate structural modifications to further optimize the compound, especially in terms of plasma protein binding. PubMed: 32886885DOI: 10.1021/acsinfecdis.0c00034 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.02 Å) |
Structure validation
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