Identification of a novel CDK9 inhibitor targeting the intramolecular hidden cavity of CDK9 induced by Tat binding

• Published in: PloS one Vol. 17; no. 11; p. e0277024
• Main Authors: Asamitsu, Kaori, Hirokawa, Takatsugu, Okamoto, Takashi
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 15.11.2022; Public Library of Science (PLoS)
• Subjects: Amino acid sequence; Amino acids; Analysis; Antiviral agents; Binding; Biology and Life Sciences; Care and treatment; Chromatography; Complications and side effects; Cyclin T1; Cyclin-dependent kinase 9; Cyclin-dependent kinases; Cytotoxicity; Elongation; Gene expression; GLP-1 receptor agonists; Glutathione; Highly active antiretroviral therapy; HIV; HIV (Viruses); Human immunodeficiency virus; Inhibitors; Kinases; Medicine and Health Sciences; Molecular dynamics; Molecular structure; Patient outcomes; Peptides; Phosphorylation; Physical Sciences; Proteins; Research and Analysis Methods; RNA polymerase; Simulation; Tat protein; Therapeutic targets; Toxicity; Japan

HIV-1 transcription is specifically augmented by a transcriptional activator complex composed of Tat, an HIV-1-encoded activator, and the host transcription elongation factor P-TEFb, which is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1. Several observations suggest that P-TEFb is an a...