Idioma:

Targeting the β‐clamp in Helicobacter pylori with FDA‐approved drugs reveals micromolar inhibition by diflunisal

Pandey, Preeti ; Verma, Vijay ; Gautam, Gunjan ; Kumari, Nilima ; Dhar, Suman Kumar ; Gourinath, Samudrala

FEBS letters, 2017-08, Vol.591 (15), p.2311-2322 [Periódico revisado por pares]

England

Texto completo disponível

Citações Citado por

Enviar para

Título:
Targeting the β‐clamp in Helicobacter pylori with FDA‐approved drugs reveals micromolar inhibition by diflunisal
Autor: Pandey, Preeti ; Verma, Vijay ; Gautam, Gunjan ; Kumari, Nilima ; Dhar, Suman Kumar ; Gourinath, Samudrala
Assuntos: Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; antibacterial activity ; Binding Sites ; competitive inhibition ; Crystallography, X-Ray ; diflunisal ; Diflunisal - chemistry ; Diflunisal - pharmacology ; DNA Ligases - metabolism ; DNA Polymerase III - antagonists & inhibitors ; DNA Polymerase III - chemistry ; DNA Polymerase III - metabolism ; DNA sliding clamp ; Drug Approval ; Drug Evaluation, Preclinical - methods ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Helicobacter pylori - drug effects ; Helicobacter pylori - enzymology ; Inhibitory Concentration 50 ; Molecular Docking Simulation ; processivity promoter ; Protein Conformation ; United States ; United States Food and Drug Administration
É parte de: FEBS letters, 2017-08, Vol.591 (15), p.2311-2322
Notas: SourceType-Other Sources-1
ObjectType-Article-2
content type line 63
ObjectType-Correspondence-1
Descrição: The β‐clamp is the processivity‐promoting factor for most of the enzymes in prokaryotic DNA replication; hence, it is a crucial drug target. In the present study, we investigated the β‐clamp from Helicobacter pylori, aiming to seek potential drug molecules against this gastric‐cancer‐causing bacterium. An in silico screening of Food and Drug Administration (FDA) approved drugs against the H. pylori β‐clamp, followed by its in vitro inhibition using a surface competition approach, yielded the drug diflunisal as a positive initial hit. Diflunisal inhibits the growth of H. pylori in the micromolar range. We determined the structure of diflunisal in complex with the β‐clamp to show that the drug binds at subsite I, which is a protein–protein interaction site. Successful identification of FDA‐approved molecules against H. pylori may lead to better and faster drug development.
Editor: England
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Targeting the β‐clamp in Helicobacter pylori with FDA‐approved drugs reveals micromolar inhibition by diflunisal

Pandey, Preeti ; Verma, Vijay ; Gautam, Gunjan ; Kumari, Nilima ; Dhar, Suman Kumar ; Gourinath, Samudrala

England

Buscando em bases de dados remotas. Favor aguardar.