ReviewBiochimica et biophysica acta. General subjects2021
The carboxylation status of osteocalcin has important consequences for its structure and dynamics.
Review in Biochimica et biophysica acta. General subjects, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Analysis of Osteocalcin Hormone Proteoforms with Vitamin D Deficiency in Patients with Diabetes Mellitus Using Multiple-Reaction Monitoring-Mass Spectrometric Immunoassay Approach.Methods and protocols · 2026Article
- Bone and muscle crosstalk in ageing and disease.Nature reviews. Endocrinology · 2025Review
- Osteocalcin in human breast milk over the course of lactation.Frontiers in endocrinology · 2025Observational
- Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.International journal of biological sciences · 2025Article
- Roles of osteocalcin in the central nervous system.CNS neuroscience & therapeutics · 2024Review
- Potential Targeting Mechanisms for Bone-Directed Therapies.International journal of molecular sciences · 2024Review
- Uncarboxylated Osteocalcin Decreases SCD1 by Activating AMPK to Alleviate Hepatocyte Lipid Accumulation.Molecules (Basel, Switzerland) · 2023Article
- Osteocalcin modulates parathyroid cell function in human parathyroid tumors.Frontiers in endocrinology · 2023Article
- Biodegradable ZnLiCa ternary alloys for critical-sized bone defect regeneration at load-bearing sites:Bioactive materials · 2021Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe carboxylation status of Osteocalcin (Ocn) not only influences formation and structure in bones but also has important endocrine functions affecting energy metabolism and expenditure. In this study, the role of γ-carboxylation of the glutamate residues in the structure-dynamics-function relationship in Ocn is investigated.
methodsThree forms of Ocn, differentially carboxylated at the Glu-17, 21 and 24 residues, along with a mutated form of Ocn carrying Glu/Ala mutations, are modeled and simulated using molecular dynamics (MD) simulation in the presence of calcium ions.
resultsCharacterization of the global conformational dynamics of Ocn, described in terms of the orientational variations within its 3-helical domain, highlights large structural variations in the non-carboxylated osteocalcin (nOcn). The bi-carboxylated Ocn (bOcn) and tri-carboxylated (tOcn) species, in contrast, display relatively rigid tertiary structures, with the dynamics of most regions strongly correlated. Radial distribution functions calculated for both bOcn and tOcn show long-range ordering of the calcium ion distribution around the carboxylated glutamate (γGlu) residues, likely playing an important role in promoting stability of these Ocns. Additionally, the same calcium ions are observed to coordinate with neighboring γGlu, better shielding their negative charges and in turn stabilizing these systems more than do the singly coordinating calcium ions observed in the case of nOcn. bOcn is also found to exhibit a more helical C-terminal structure, that has been shown to activate its cellular receptor GPRC6A, highlighting the allosteric role of Ocn carboxylation in modulating the stability and binding potential of the active C-terminal.
conclusionsThe carboxylation status of Ocn as well and its calcium coordination appear to have a direct influence on Ocn structure and dynamics, possibly leading to the known differences in Ocn biological function. GENERAL SIGNIFICANCE: Modification of Ocn sequence or its carboxylation state may provide the blueprint for developing high-affinity peptides targeting its cellular receptor GPRC6A, with therapeutic potential for treatment of metabolic disorders.
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