{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Conley JF"],"funding":["NCATS NIH HHS","NIGMS NIH HHS"],"pagination":["5795-5808"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11840593"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(6)"],"pubmed_abstract":["Eukaryotic initiation factor 4A-1 (eIF4A1) is an ATP-dependent RNA helicase that unwinds 5'-UTR mRNA secondary structures to facilitate cap-dependent translation initiation. Rocaglates, a class of natural products typified by rocaglamide A (RocA), possess antineoplastic and anti-infectious activity mediated by their interaction with eIF4A1. Rocaglates inhibit cap-dependent translation initiation by \"clamping\" eIF4A1 onto polypurine RNA, which impedes ribosome scanning. A novel class of rocaglate derivatives, amidino-rocaglates (ADRs) which feature an amidine ring fused to the rocaglate core, is particularly effective at promoting eIF4A1-RNA-clamping compared to other rocaglate congeners. Herein, we present the X-ray crystal structure of an ADR in complex with eIF4A1, the nonhydrolyzable AT"],"journal":["ACS omega"],"pubmed_title":["Structural Basis for the Improved RNA Clamping of Amidino-Rocaglates to eIF4A1."],"pmcid":["PMC11840593"],"funding_grant_id":["R35 GM118173","P30 GM133893","U01 TR002625"],"pubmed_authors":["Pelletier J","Allen KN","Conley JF","McNeely JH","Porco JA","Brown LE"],"additional_accession":[]},"is_claimable":false,"name":"Structural Basis for the Improved RNA Clamping of Amidino-Rocaglates to eIF4A1.","description":"Eukaryotic initiation factor 4A-1 (eIF4A1) is an ATP-dependent RNA helicase that unwinds 5'-UTR mRNA secondary structures to facilitate cap-dependent translation initiation. Rocaglates, a class of natural products typified by rocaglamide A (RocA), possess antineoplastic and anti-infectious activity mediated by their interaction with eIF4A1. Rocaglates inhibit cap-dependent translation initiation by \"clamping\" eIF4A1 onto polypurine RNA, which impedes ribosome scanning. A novel class of rocaglate derivatives, amidino-rocaglates (ADRs) which feature an amidine ring fused to the rocaglate core, is particularly effective at promoting eIF4A1-RNA-clamping compared to other rocaglate congeners. Herein, we present the X-ray crystal structure of an ADR in complex with eIF4A1, the nonhydrolyzable AT","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-01T13:00:58.108Z","creation":"2025-04-04T13:11:19.479Z"},"accession":"S-EPMC11840593","cross_references":{"pubmed":["39989799"],"doi":["10.1021/acsomega.4c09421"]}}