{"doi":"10.1038/emboj.2008.186","title":"Structural insights into mechanism and specificity of O‐GlcNAc transferase","abstract":null,"journal":"The EMBO Journal","year":2008,"id":635355,"datarank":0.7193685818395114,"base_score":4.795790545596741,"endowment":4.795790545596741,"self_citation_contribution":0.7193685818395114,"citation_network_contribution":0.0,"self_endowment_contribution":0.7193685818395114,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":120,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1648359,"name":"Ramon Hurtado‐Guerrero","orcid":null,"position":1,"is_corresponding":false},{"id":1648362,"name":"Shalini Pathak","orcid":null,"position":2,"is_corresponding":false},{"id":1648365,"name":"Alexander W Schüttelkopf","orcid":null,"position":3,"is_corresponding":false},{"id":1648366,"name":"Vladimir Borodkin","orcid":null,"position":4,"is_corresponding":false},{"id":1648368,"name":"Sharon M Shepherd","orcid":null,"position":5,"is_corresponding":false},{"id":1648370,"name":"Adel F M Ibrahim","orcid":null,"position":6,"is_corresponding":false},{"id":1648372,"name":"Daan M F van Aalten","orcid":null,"position":7,"is_corresponding":false},{"id":1648356,"name":"Andrew J Clarke","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structural insights into mechanism and specificity of O‐GlcNAc transferase","abstract":"Post-translational modification of protein serines/threonines with N-acetylglucosamine (O-GlcNAc) is dynamic, inducible and abundant, regulating many cellular processes by interfering with protein phosphorylation. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase, both encoded by single, essential, genes in metazoan genomes. It is not understood how OGT recognises its sugar nucleotide donor and performs O-GlcNAc transfer onto proteins/peptides, and how the enzyme recognises specific cellular protein substrates. Here, we show, by X-ray crystallography and mutagenesis, that OGT adopts the (metal-independent) GT-B fold and binds a UDP-GlcNAc analogue at the bottom of a highly conserved putative peptide-binding groove, covered by a mobile loop. Strikingly, the tetratricopeptide repeats (TPRs) tightly interact with the active site to form a continuous 120 A putative interaction surface, whereas the previously predicted phosphatidylinositide-binding site locates to the opposite end of the catalytic domain. On the basis of the structure, we identify truncation/point mutants of the TPRs that have differential effects on activity towards proteins/peptides, giving first insights into how OGT may recognise its substrates.","is_dataset_classified":null,"base_score":4.795790545596741,"endowment":4.795790545596741,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18818698","pmcid":"PMC2556091","openalex_id":"https://openalex.org/W1975557255","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":2,"fwci":4.4189,"citation_percentile":0.95239026,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":7},{"year":2014,"count":8},{"year":2015,"count":9},{"year":2016,"count":4},{"year":2017,"count":6},{"year":2018,"count":3},{"year":2019,"count":5},{"year":2020,"count":5},{"year":2021,"count":7},{"year":2022,"count":6},{"year":2023,"count":4},{"year":2024,"count":6},{"year":2025,"count":7}],"oa_status":"green","license":"CC BY NC ND","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2556091","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2556091","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Femboj.2008.186","host_type":"publisher"},{"url":"https://link.springer.com/content/pdf/10.1038/emboj.2008.186.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1038/emboj.2008.186","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full/10.1038/emboj.2008.186","host_type":"publisher"},{"url":"https://doi.org/10.1038/emboj.2008.186","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18818698","host_type":"repository"},{"url":"https://discovery.dundee.ac.uk/en/publications/33d23365-dbf1-462f-92f3-2c08ed65bdd0","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2556091","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2556091?pdf=render","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/pmc2556091?pdf=render","host_type":""},{"url":"http://dx.doi.org/10.1038/emboj.2008.186","host_type":""},{"url":"https://dx.doi.org/10.1038/emboj.2008.186","host_type":""},{"url":"https://doi.org/https://doi.org/10.1038/emboj.2008.186","host_type":""}],"fields_of_study":["Glycosylation and Glycoproteins Research","Carbohydrate Chemistry and Synthesis","Biochemical and Molecular Research","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Amino Acid Sequence","Animals","Humans","Models, Biological","Molecular Conformation","Molecular Sequence Data","Phosphorylation","Protein Binding","Protein Processing, Post-Translational","Substrate Specificity","Xenopus","Signal Transduction","N-Acetylglucosaminyltransferases","Sequence Homology, Amino Acid","Crystallography, X-Ray"],"keywords":["Biology","Tetratricopeptide","Transferase","Mutagenesis","Biochemistry","Mutant","Phosphorylation","Gene","Cell biology","Enzyme","570","Substrate specificity","Xenopus","Molecular Sequence Data","Glycobiology","Molecular Conformation","Signal transduction","Crystallography, X-Ray","N-Acetylglucosaminyltransferases","Linked GlcNAc","Models, Biological","Article","N-acetylglucosamine deacetylase","Animals","Humans","Amino Acid Sequence","Sequence Homology, Amino Acid","Tetratricopeptide repeats","Insulin resistance","Mutational analysis","UDP-GlcNAc","Protein phosphatase","Crystal structures","O-GlcNAc","Protein structure","Cytosolic proteins","Protein Processing, Post-Translational","Protein Binding"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"uniprot"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:58:26.755402Z","pmid":null,"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":[]}