About: Virtual High-Throughput Screening Identifies Mycophenolic Acid as a Novel RNA Capping Inhibitor

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About: Virtual High-Throughput Screening Identifies Mycophenolic Acid as a Novel RNA Capping Inhibitor Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Virtual High-Throughput Screening Identifies Mycophenolic Acid as a Novel RNA Capping Inhibitor
Creator	Bisaillon, Martin Bougie, Isabelle Despins, Simon Mata, Juan Tremblay-Lé, Maude
source	PMC
abstract	The RNA guanylyltransferase (GTase) is involved in the synthesis of the (m7)Gppp-RNA cap structure found at the 5′ end of eukaryotic mRNAs. GTases are members of the covalent nucleotidyl transferase superfamily, which also includes DNA and RNA ligases. GTases catalyze a two-step reaction in which they initially utilize GTP as a substrate to form a covalent enzyme-GMP intermediate. The GMP moiety is then transferred to the diphosphate end of the RNA transcript in the second step of the reaction to form the Gppp-RNA structure. In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors. Using this approach, we demonstrate that mycophenolic acid (MPA) can inhibit the GTase reaction by preventing the catalytic transfer of the GMP moiety onto an acceptor RNA. As such, MPA represents a novel type of inhibitor against RNA guanylyltransferases that inhibits the second step of the catalytic reaction. Moreover, we show that the addition of MPA to S. cerevisiae cells leads to a reduction of capped mRNAs. Finally, biochemical assays also demonstrate that MPA can inhibit DNA ligases through inhibition of the second step of the reaction. The biological implications of these findings for the MPA-mediated inhibition of members of the covalent nucleotidyl superfamily are discussed.
has issue date	2011-09-15(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0024806
bibo:pmid	21935470
has license	cc-by
sha1sum (hex)	54b6c7145a0f7743409d5590780ef253152873dd
schema:url	https://doi.org/10.1371/journal.pone.0024806
resource representing a document's title	Virtual High-Throughput Screening Identifies Mycophenolic Acid as a Novel RNA Capping Inhibitor
has PubMed Central identifier	PMC3174198
has PubMed identifier	21935470
schema:publication	PLoS One
resource representing a document's body	covid:54b6c7145a0f7743409d5590780ef253152873dd#body_text
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