title: Deciphering the protein translation inhibition and coping mechanism of trichothecene toxin in resistant fungi.
abstract: In modern times for combating the deleterious soil microbes for improved sustainable agricultural practices, there is a need to have a proper understanding of the plant-microbe interactions present in the rhizospheric microbiome of the plant roots. In the present study, the interactions of trichodermin with petidyltransferase centre of ribosomal complex was studied by molecular dynamics and in silico interaction methods to demonstrate its mechanism of action and to decipher the possible reason how it may inhibit protein synthesis at the ribosomal complex. Further we have illustrated how trichodermin resistance protein (60S ribosomal protein L3) helps to overcome the deleterious effects of trichothecene compounds like trichodermin. Normal mode analysis of trichodermin resistance protein and 25S rRNA that constitutes the petidyltransferase centre showed that the W-finger region of the protein moved towards 25S rRNA. Further analysis of molecular dynamics simulation time frames showed that several intermediate states of large motions of the protein molecules towards the 25S rRNA which finally blocks the binding pocket of the trichodermin. It indicated that this protein not only changes the local environment and conformation of the petidyltransferase centre but also restrain trichodermin from binding to the 25S rRNA at the petidyltransferase centre.
authors: School of Earth and Environmental Sciences, Central University of Himachal Pradesh, Kangra, Himachal Pradesh, 176206, India.
authors: Indu
authors: I
authors: Kumari
authors: School of Earth and Environmental Sciences, Central University of Himachal Pradesh, Kangra, Himachal Pradesh, 176206, India. Electronic address: mushtaq.cuhp@gmail.com.
authors: Mushtaq
authors: M
authors: Ahmed
authors: School of Life Sciences, Central University of Himachal Pradesh, Kangra, Himachal Pradesh, 176206, India. Electronic address: yusuf@cuhimachal.ac.in.
authors: Yusuf
authors: Y
authors: Akhter
mesh_terms: D025141:Drug Resistance, Fungal; D008958:Models, Molecular; D010458:Peptidyl Transferases / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011487:Protein Conformation; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D014255:Trichothecenes / Q000378:metabolism / Q000633:toxicity*
chemical_list: D014255:Trichothecenes; D010458:Peptidyl Transferases
keywords: Ribosomal complex; Trichoderma; Trichodermin; Trichodermin resistance protein; Yeast