A Novel Antifungal Compound Z-705 Specifically Inhibits Protein Kinase C of Filamentous Fungi.

A Novel Antifungal Compound Z-705 Specifically Inhibits Protein Kinase C of Filamentous Fungi. Appl Environ Microbiol. 2019 Mar 22;: Authors: Sugahara A, Yoshimi A, Shoji F, Fujioka T, Kawai K, Umeyama H, Komatsu K, Enomoto M, Kuwahara S, Hagiwara D, Katayama T, Horiuchi H, Miyazawa K, Nakayama M, Abe K Abstract The cell wall integrity signaling (CWIS) pathway is involved in fungal cell-wall biogenesis. This pathway is composed of sensor proteins, protein kinase C (PKC), and the MAP kinase pathway, and controls the transcription of many cell-wall related genes. PKC plays a pivotal role in this pathway; deficiency in PkcA in the model filamentous fungus Aspergillus nidulans and in MgPkc1 in the rice blast fungus Magnaporthe grisea is lethal. This suggests that PKC in filamentous fungi is a potential target for antifungal agents. In the present study, to search for MgPkc1 inhibitors, we carried out in silico screening by three-dimensional structural modeling and performed growth inhibition tests for M. grisea on agar plates. From approximately 800,000 candidate compounds, we selected Z-705 and evaluated its inhibitory activity against chimeric PKC expressed in Saccharomyces cerevisiae in which the kinase domain of native S. cerevisiae PKC was replaced with those of PKCs of filamentous fungi. Transcriptional analysis of MLP1, which encodes a downstream factor of PKC in S. cerevisiae, and phosphorylation analysis of the mitogen-activated...
Source: Applied and Environmental Microbiology - Category: Microbiology Authors: Tags: Appl Environ Microbiol Source Type: research