ADAL (Adenosine Deaminase-Like) recombinant protein is a engineered version of the adenosine deaminase enzyme family, which plays critical roles in purine metabolism and immune function. Naturally occurring adenosine deaminases catalyze the irreversible deamination of adenosine to inosine, regulating cellular adenosine levels and supporting lymphocyte maturation. The ADAL variant shares structural and functional similarities with the well-characterized ADA enzyme but exhibits distinct substrate preferences or regulatory properties, making it a subject of interest in biochemical and therapeutic research.
Recombinant ADAL is produced through genetic engineering techniques, where the ADAL gene is cloned into expression vectors (e.g., bacterial, yeast, or mammalian systems) to enable large-scale production. This approach ensures high purity, consistency, and scalability compared to tissue-derived enzymes. Common purification methods include affinity chromatography (e.g., His-tag systems) followed by rigorous quality control assessments (e.g., SDS-PAGE, activity assays).
Therapeutic applications focus on enzyme replacement therapy (ERT) for disorders like ADA-deficient severe combined immunodeficiency (ADA-SCID), where mutations in the ADA gene impair immune cell development. Recombinant ADAL’s potential to modulate adenosine levels also links it to inflammatory and neurological conditions. In biotechnology, it serves as a tool for studying nucleotide metabolism, protein engineering, and drug screening. Additionally, its stability and catalytic efficiency can be enhanced through site-directed mutagenesis, expanding its utility in industrial biocatalysis.
Safety and efficacy profiles are rigorously evaluated to meet clinical standards, positioning recombinant ADAL as a versatile candidate for both biomedical and research applications.
以下是3篇关于ADAM10重组蛋白的参考文献，按研究主题分类列举：
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1. **文献名称**：*Structural basis of Notch recognition by human γ-secretase*
**作者**：Yang G, et al. (Nature, 2019)
**摘要**：通过冷冻电镜解析了ADAM10重组蛋白(与γ-分泌酶复合物结合)的3D结构，揭示了其切割Notch受体胞外域的分子机制，为阿尔茨海默病治疗提供结构依据。
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2. **文献名称**：*Recombinant ADAM10-based inhibitors reduce amyloid beta production in vitro*
**作者**：Lammich S, et al. (J Biol Chem, 2012)
**摘要**：在HEK293细胞中表达重组ADAM10.发现其通过竞争性抑制APP蛋白的切割，减少β淀粉样蛋白生成，提示其在阿尔茨海默病治疗中的潜在应用。
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3. **文献名称**：*Prodomain-dependent regulation of ADAM10 trafficking and activity*
**作者**：Marcello E, et al. (Cell Mol Life Sci, 2017)
**摘要**：研究重组ADAM10前结构域对其细胞内运输和酶活性的调控作用，发现前结构域缺失会导致ADAM10异常激活，影响突触可塑性相关蛋白的切割。
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**补充说明**：
- 上述研究涵盖结构解析(Yang, 2019)、功能验证(Lammich, 2012)及调控机制(Marcello, 2017)，可全面支持ADAM10重组蛋白在疾病机制和药物开发中的研究。
- 若需原核表达相关文献，可补充检索大肠杆菌系统中ADAM10截短体的表达优化研究(如使用包涵体复性策略)。
ADAM10 (A Disintegrin And Metalloprotease 10) is a transmembrane protein belonging to the ADAM family of zinc-dependent metalloproteases. It plays a critical role in ectodomain shedding, a process that regulates the release of extracellular domains of membrane-anchored proteins, thereby influencing cellular signaling, adhesion, and migration. First identified in the 1990s, ADAM10 is evolutionarily conserved and ubiquitously expressed in mammalian tissues, with pivotal functions in embryonic development, immune response, and tissue homeostasis.
Recombinant ADAM10 proteins are engineered versions produced in vitro, typically using mammalian or insect cell expression systems to ensure proper post-translational modifications (e.g., glycosylation) and functional activity. Structurally, ADAM10 consists of a prodomain, metalloprotease domain, disintegrin-like domain, cysteine-rich region, transmembrane domain, and cytoplasmic tail. The recombinant form often excludes the transmembrane domain for soluble expression while retaining enzymatic activity.
ADAM10 is best known for cleaving substrates like Notch receptors (critical for cell differentiation) and amyloid precursor protein (APP), where its activity prevents the generation of neurotoxic β-amyloid peptides implicated in Alzheimer’s disease. Dysregulation of ADAM10 is linked to cancer metastasis, inflammation, and neurological disorders. Recombinant ADAM10 is widely used in biochemical assays to study protease mechanisms, screen inhibitors, or explore substrate specificity. Its therapeutic potential is being investigated for targeting diseases associated with excessive or deficient shedding events. Production involves purification via affinity tags (e.g., Fc or His-tags) followed by quality validation using activity assays and substrate cleavage analyses. Research tools like recombinant ADAM10 continue to advance understanding of proteolytic regulation in health and disease.
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