6VJS

Escherichia coli RNA polymerase and ureidothiophene-2-carboxylic acid complex

6VJS の概要

• エントリーDOI: 10.2210/pdb6vjs/pdb
• 分子名称: DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (8 entities in total)
• 機能のキーワード: rna polymerase transcription, transcription
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 920596.41

構造登録者

Murakami, K.S.,Molodtsov, V. (登録日: 2020-01-17, 公開日: 2020-10-07, 最終更新日: 2023-10-11)

主引用文献

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

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: 32886885
DOI: 10.1021/acsinfecdis.0c00034

実験手法

X-RAY DIFFRACTION (4.02 Å)