ArticleThe Journal of biological chemistry2009
Missense mutations that cause Bruck syndrome affect enzymatic activity, folding, and oligomerization of lysyl hydroxylase 2.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Extending the global landscape of Bruck syndrome: Case series of Indonesian and Ukrainian patients with PLOD2 pathogenic variants and literature review.Bone reports · 2026Article
- Significant improvement following intravenous zoledronate therapy in Bruck syndrome 2 due to a rareJCEM case reports · 2026Article
- Discovery of Glucose Metabolism-Associated Genes in Neuropathic Pain: Insights from Bioinformatics.International journal of molecular sciences · 2024Article
- Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in theInternational journal of molecular sciences · 2024Article
- Hypoxia-induced PLOD2 promotes clear cell renal cell carcinoma progression via modulating EGFR-dependent AKT pathway activation.Cell death & disease · 2023Article
- Genetic Analysis and Functional Study of a Pedigree With Bruck Syndrome Caused byFrontiers in pediatrics · 2022Article
- Exome sequencing identifies procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 mutations in primary congenital and juvenile glaucoma.Indian journal of ophthalmology · 2021Article
- Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound HeterozygousJBMR plus · 2021Article
- Exome Sequencing Reveals a Phenotype Modifying Variant in ZNF528 in Primary Osteoporosis With a COL1A2 Deletion.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Article
- Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3.Nature communications · 2018Article
- Bioinspired Hydrogels to Engineer Cancer Microenvironments.Annual review of biomedical engineering · 2017Review
- A Chaperone Complex Formed by HSP47, FKBP65, and BiP Modulates Telopeptide Lysyl Hydroxylation of Type I Procollagen.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- Hypoxia and TGF-β1 induced PLOD2 expression improve the migration and invasion of cervical cancer cells by promoting epithelial-to-mesenchymal transition (EMT) and focal adhesion formation.Cancer cell international · 2017Article
- Loss of Type I Collagen Telopeptide Lysyl Hydroxylation Causes Musculoskeletal Abnormalities in a Zebrafish Model of Bruck Syndrome.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Disentangling mechanisms involved in collagen pyridinoline cross-linking: The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Co-operative intermolecular kinetics of 2-oxoglutarate dependent dioxygenases may be essential for system-level regulation of plant cell physiology.Frontiers in plant science · 2015Article
- Connective tissue alterations in Fkbp10-/- mice.Human molecular genetics · 2014Article
- Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Hypoxia-dependent modification of collagen networks promotes sarcoma metastasis.Cancer discovery · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bruck syndrome is a rare autosomal recessive connective tissue disorder characterized by fragile bones, joint contractures, scoliosis, and osteoporosis. The telopeptides of bone collagen I are underhydroxylated in these patients, leading to abnormal collagen cross-linking. Three point mutations in lysyl hydroxylase (LH) 2, the enzyme responsible for the hydroxylation of collagen telopeptides, have been identified in Bruck syndrome. As none of them affects the residues known to be critical for LH activity, we studied their consequences at the molecular level by analyzing the folding and catalytic properties of the corresponding mutant recombinant polypeptides. Folding and oligomerization of the R594H and G597V mutants were abnormal, and their activity was reduced by >95% relative to the wild type. The T604I mutation did not affect the folding properties, although the mutant retained only approximately 8% activity under standard assay conditions. As the reduced activity was caused by a 10-fold increase in the K(m) for 2-oxoglutarate, the mutation interferes with binding of this cosubstrate. In the presence of a saturating 2-oxoglutarate concentration, the activity of the T604I mutant was approximately 30% of that of the wild type. However, the T604I mutant did not generate detectable amounts of hydroxylysine in the N-terminal telopeptide of a recombinant procollagen I chain when coexpressed in insect cells. The low activity of the mutant LH2 polypeptides is in accordance with the markedly reduced extent of collagen telopeptide hydroxylation in Bruck syndrome, with consequent changes in the cross-linking of collagen fibrils and severe abnormalities in the skeletal structures.
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