γ-Carboxylation Analysis Service

γ-Carboxylation is a vitamin K–dependent enzymatic reaction catalyzed by γ-glutamyl carboxylase. The biological significance of this process is vast, spanning hemostasis, mineralization, and disease pathology. MtoZ Biolabs offers end-to-end γ-Carboxylation Analysis Services to study γ-carboxylation events in both targeted and proteome-wide contexts. 

1. Target Protein γ-Carboxylation Analysis

For specific protein studies, MtoZ Biolabs provides targeted γ-carboxylation analysis to identify modification sites and quantify their levels. This service uses high-resolution LC-MS/MS and antibody-based techniques to achieve precise, site-specific detection, enabling functional analysis of γ-carboxylation in key proteins involved in coagulation, bone metabolism, and disease processes.

2. γ-Carboxylation Proteomics

For broader, discovery-driven projects, our γ-carboxylation proteomics workflow enables proteome-wide profiling of γ-carboxylated proteins. We provide global modification maps, quantitative comparisons, and bioinformatics-driven pathway analysis to uncover how γ-carboxylation impacts cellular functions and regulatory networks.

What is γ-Carboxylation?

γ-Carboxylation refers to the vitamin K–dependent conversion of specific glutamate residues to γ-carboxyglutamate (Gla), a residue capable of binding calcium ions with high affinity. This modification is indispensable for the biological function of coagulation factors II, VII, IX, and X, as well as proteins such as osteocalcin, matrix Gla protein, and Gas6.

Source: Wikipedia

Figure 1. Vitamin K-Dependent γ-Carboxylation Mechanism

Mechanistically, γ-carboxylation ensures proper calcium-mediated protein conformation, allowing these proteins to interact with phospholipid membranes and fulfill their physiological roles. Dysregulation of γ-carboxylation has been linked to bleeding disorders, vascular calcification, osteoporosis, and certain malignancies. Given its central role in both physiology and pathology, γ-carboxylation is not only a subject of basic research but also an important focus in biomarker discovery and drug development.

Despite its importance, γ-carboxylation remains technically challenging to study. The modification is subtle, often present at low stoichiometry, and difficult to distinguish from other acidic residue modifications. Mass spectrometry combined with enrichment and orthogonal techniques now provides a reliable avenue to identify and quantify γ-carboxylation with confidence.

Analysis Workflow

1. Sample Preparation

Proteins from tissues, biofluids, or cultured cells are extracted and digested into peptides under optimized conditions that preserve γ-carboxylation.

2. Enrichment of γ-Carboxylated Peptides

Affinity enrichment strategies, including antibody-based capture and chemical derivatization, are employed to selectively isolate modified peptides.

3. Detection

• High-performance LC systems coupled with Orbitrap LC-MS/MS instruments provide sensitive, site-specific detection of γ-carboxylation events.

• Complementary NMR spectroscopy offers structural insights into calcium-binding domains.

• Targeted methods such as PRM and MRM enable precise quantification of γ-carboxylation dynamics under different conditions or treatments.

• Antibody-based immunoassays, including Western blotting and ELISA, provide orthogonal validation of MS results for confidence and reproducibility.

4. Bioinformatics Analysis

Computational pipelines integrate modification data with pathway analysis, functional annotations, and cross-modification crosstalk, linking γ-carboxylation to biological outcomes.

Sample Submission Suggestions

1. Sample Types: Cell lysates, tissue extracts, purified proteins, plasma, or serum. For other sample types, please contact us in advance for tailored preparation guidance.

2. Storage: Store at -80°C; avoid repeated freeze-thaw cycles.

3. Shipping: Send frozen samples on dry ice; lyophilized proteins may be shipped at room temperature.

Service Advantages

✅ Advancement: The γ-Carboxylation Analysis Service is supported by an advanced analytical platform that ensures accurate, reproducible, and cutting-edge solutions for modification research.

✅ High Quality: By integrating all proteomics datasets through our AI-driven bioinformatics analysis platform, we deliver comprehensive, high-quality data reports that provide clear biological interpretation.

✅ Comprehensiveness: We offer one-stop services covering the entire workflow, from sample preparation and enrichment to detection, validation, and functional annotation.

✅ Professionalism: Our experienced scientific team provides not only accurate analysis but also professional technical support, ensuring reliable data interpretation aligned with research objectives.

✅ Customization: Services are fully adaptable to the specific goals of each project, with flexible strategies designed to meet diverse sample types and experimental requirements.

Applications

1. Blood Coagulation Research

Investigating γ-carboxylation in coagulation factors to study bleeding disorders and anticoagulant mechanisms.

2. Bone and Mineralization Studies

Profiling osteocalcin and matrix Gla protein to understand their role in skeletal biology and vascular calcification.

3. Cardiovascular and Metabolic Diseases

Linking altered γ-carboxylation to atherosclerosis, diabetes, and vascular pathology.

4. Oncology Research

Exploring the regulatory function of γ-carboxylated proteins in cancer signaling and progression.

5. Drug Development

Supporting therapeutic design targeting vitamin K pathways, anticoagulants, and bone health treatments.

6. Biomarker Discovery

Identifying γ-carboxylation signatures as potential diagnostic or prognostic markers in clinical research.

FAQ

Q1: How does MtoZ Biolabs ensure reliable detection of low-abundance γ-carboxylated proteins?

A1: We combine optimized enrichment strategies with high-resolution mass spectrometry and orthogonal validation approaches. This ensures sensitive detection of low-abundance γ-carboxylated peptides and minimizes false positives.

Q2: Can γ-carboxylation analysis be combined with other PTM studies?

A2: Yes. Our workflows can be integrated with phosphorylation, glycosylation, acetylation, or other PTM profiling to study cross-talk between γ-carboxylation and other regulatory modifications at the proteome level.

Our comprehensive solutions allow researchers to explore γ-carboxylation with accuracy, reproducibility, and depth, supporting discoveries from mechanistic biology to therapeutic development. If you are interested in our γ-Carboxylation Analysis Service, please feel free to contact us.