biostudies-literatureScietti LGiovanni Armenise-Harvard FoundationMizutani Foundation for GlycoscienceMinistero Dell’Istruzione, dell’Università e Della RicercaEuropean CommissionAssociazione Italiana per la Ricerca Sul Cancro876352https://www.ebi.ac.uk/biostudies/studies/S-EPMC9453210biostudies-literatureUnknown9Multifunctional human collagen lysyl hydroxylase (LH/PLOD) enzymes catalyze post-translational hydroxylation and subsequent glycosylation of collagens, enabling their maturation and supramolecular organization in the extracellular matrix (ECM). Recently, the overexpression of LH/PLODs in the tumor microenvironment results in abnormal accumulation of these collagen post-translational modifications, which has been correlated with increased metastatic progression of a wide variety of solid tumors. These observations make LH/PLODs excellent candidates for prospective treatment of aggressive cancers. The recent years have witnessed significant research efforts to facilitate drug discovery on LH/PLODs, including molecular structure characterizations and development of reliable high-throughput enFrontiers in molecular biosciencesA Fe²⁺-dependent self-inhibited state influences the druggability of human collagen lysyl hydroxylase (LH/PLOD) enzymes.PMC9453210to FFH2020-MSCA-IF COTETHERS (n. 745934) to AC200039 to FFMFAG 20075 to FFFumagalli MDe Giorgi FMattoteia DChiapparino AFaravelli SColombo GForneris FMoroni ENegro LDe Marco MScietti LSerapian SAfalseA Fe²⁺-dependent self-inhibited state influences the druggability of human collagen lysyl hydroxylase (LH/PLOD) enzymes.Multifunctional human collagen lysyl hydroxylase (LH/PLOD) enzymes catalyze post-translational hydroxylation and subsequent glycosylation of collagens, enabling their maturation and supramolecular organization in the extracellular matrix (ECM). Recently, the overexpression of LH/PLODs in the tumor microenvironment results in abnormal accumulation of these collagen post-translational modifications, which has been correlated with increased metastatic progression of a wide variety of solid tumors. These observations make LH/PLODs excellent candidates for prospective treatment of aggressive cancers. The recent years have witnessed significant research efforts to facilitate drug discovery on LH/PLODs, including molecular structure characterizations and development of reliable high-throughput en2022-01-01T00:00:00Z20222026-05-28T05:41:08.108Z2025-02-19T04:38:59.664ZS-EPMC94532103609004710.3389/fmolb.2022.876352