ArticleProceedings of the National Academy of Sciences of the United States of America2018
Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 89 citations in OpenAlex.
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Hydrogen sulfide generated by cystathionine gamma lyase inhibits lysyl oxidase and protects against calcific tendinopathy.Journal of orthopaedic translation · 2026Article
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- Integrated genetic identification and molecular dynamics simulations in a novelFrontiers in genetics · 2026Article
- Covalent Inhibitor Screening for Targeting LOXL2: Studied by Virtual Screening and Experimental Validation.Recent patents on anti-cancer drug discovery · 2026Article
- Integrating multi-omics to reveal the molecular mechanism of lipid metabolism regulated by a splice variant of Lysyl-oxidase like-2, LOXL2Δ13.Communications biology · 2025Article
- Multi-target-directed therapeutic strategies for Alzheimer's disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition.Chemical science · 2025Review
- Reactive Oxygen Species in Asthma: Regulators of Macrophage Polarization and Therapeutic Implications: A Narrative Review.Journal of asthma and allergy · 2025Review
- Lysyl Oxidase as a Target to Reduce Graft Failure Post Solid Organ Transplantation, a Potential Target for Novel Treatment.Current medicinal chemistry · 2025Review
- Characterization and priming of equine muscle-derived mesenchymal stem cells to enhance their anti-inflammatory and immunomodulatory profiles.Frontiers in veterinary science · 2025Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Glycosylation Modulates the Structure and Functions of Collagen: A Review.Molecules (Basel, Switzerland) · 2024Review
- Identification and validation of targets of swertiamarin on idiopathic pulmonary fibrosis through bioinformatics and molecular docking-based approach.BMC complementary medicine and therapies · 2023Article
- Polyphenol-based targeted therapy for oral submucous fibrosis.Inflammopharmacology · 2023Article
- LOXL2 in Cancer: A Two-Decade Perspective.International journal of molecular sciences · 2023Review
- Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging.ChemMedChem · 2023Review
- Exploring the Interplay between Polyphenols and Lysyl Oxidase Enzymes for Maintaining Extracellular Matrix Homeostasis.International journal of molecular sciences · 2023Review
- [Relationship between trace elements in synovial fluid and cartilage and severity of knee osteoarthritis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2023Article
- Lysyl oxidase-like 2 processing by factor Xa modulates its activity and substrate preference.Communications biology · 2023Article
- Protein disulfide isomerase A3 activity promotes extracellular accumulation of proteins relevant to basal breast cancer outcomes in human MDA-MB-A231 breast cancer cells.American journal of physiology. Cell physiology · 2023Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
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Abstract
Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) -dependent amine oxidase, catalyze the oxidative deamination of lysine residues of extracellular matrix (ECM) proteins such as elastins and collagens and generate aldehyde groups. The oxidative deamination of lysine represents the foundational step for the cross-linking of elastin and collagen and thus is crucial for ECM modeling. Despite their physiological significance, the structure of this important family of enzymes remains elusive. Here we report the crystal structure of human lysyl oxidase-like 2 (hLOXL2) at 2.4-Å resolution. Unexpectedly, the copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis confirms that copper loading robustly activates hLOXL2 and supports LTQ formation. Furthermore, the LTQ precursor residues in the structure are distanced by 16.6 Å, corroborating the notion that the present structure may represent a precursor state and that pronounced conformational rearrangements would be required for protein activation. The structure presented here establishes an important foundation for understanding the structure-function relationship of LOX proteins and will facilitate LOX-targeting drug discovery.
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