{"doi":"10.1093/plcell/koad299","title":"Structure-based virtual screening identifies small-molecule inhibitors of O-fucosyltransferase SPINDLY in Arabidopsis","abstract":"Protein O-glycosylation is a nutrient signaling mechanism that plays an essential role in maintaining cellular homeostasis across different species. In plants, SPINDLY (SPY) and SECRET AGENT (SEC) posttranslationally modify hundreds of intracellular proteins with O-fucose and O-linked N-acetylglucosamine, respectively. SPY and SEC play overlapping roles in cellular regulation, and loss of both SPY and SEC causes embryo lethality in Arabidopsis (Arabidopsis thaliana). Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a SPY O-fucosyltransferase inhibitor (SOFTI). Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. In vitro assays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and elicited phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defective sugar-dependent growth. In contrast, SOFTI did not visibly affect the spy mutant. Similarly, SOFTI inhibited the sugar-dependent growth of tomato (Solanum lycopersicum) seedlings. These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor that can be used as a chemical tool for functional studies of O-fucosylation and potentially for agricultural management.","journal":"The Plant Cell","year":2023,"id":343742,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1081778,"name":"Hongming Zhao","orcid":"0009-0000-4942-9738","position":1,"is_corresponding":false},{"id":660167,"name":"Zhenzhen Zhang","orcid":"0000-0003-1617-8543","position":2,"is_corresponding":false},{"id":576215,"name":"Yang Bi","orcid":"0000-0003-1270-1747","position":3,"is_corresponding":false},{"id":250309,"name":"Qiuhua Yang","orcid":"0000-0002-5582-3771","position":4,"is_corresponding":false},{"id":613211,"name":"G. Guo","orcid":null,"position":5,"is_corresponding":false},{"id":1081779,"name":"Hongliang Zhang","orcid":"0000-0002-3002-798X","position":6,"is_corresponding":false},{"id":1081780,"name":"Hongwei Guo","orcid":"0000-0002-7883-9477","position":7,"is_corresponding":false},{"id":1081781,"name":"Kai Jiang","orcid":"0000-0001-9901-5293","position":8,"is_corresponding":false},{"id":292355,"name":"Zhiyong Wang","orcid":"0000-0003-4602-3390","position":9,"is_corresponding":false},{"id":1081777,"name":"Yalikunjiang Aizezi","orcid":"0000-0002-6737-001X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T01:11:26.556051Z","pmid":"38124350","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}