Recombinant Human CSMD1 protein

IMPDH2 (Inosine-5'-monophosphate dehydrogenase isoform 2) is a key enzyme in the de novo biosynthesis of guanine nucleotides, catalyzing the NAD-dependent oxidation of inosine-5'-monophosphate (IMP) to xanthosine-5'-monophosphate (XMP), a rate-limiting step in GTP production. As one of two isoforms in humans (IMPDH1 and IMPDH2), IMPDH2 is highly expressed in proliferating cells, including cancer cells and activated lymphocytes, making it a critical target for immunosuppressive and anticancer therapies. Its activity supports cellular processes requiring rapid nucleotide turnover, such as DNA/RNA synthesis and signaling.

Recombinant IMPDH2 protein is produced via genetic engineering, typically using bacterial (e.g., E. coli) or mammalian expression systems, to enable large-scale studies of its structure, function, and inhibition. Purified recombinant IMPDH2 retains enzymatic activity and is widely used in biochemical assays, inhibitor screening, and structural studies (e.g., X-ray crystallography) to elucidate mechanisms of catalysis and regulation. Notably, IMPDH2 forms tetramers and undergoes conformational changes during substrate binding, features that have been mapped using recombinant variants.

Pharmaceutically, IMPDH2 is a validated drug target. Mycophenolic acid (MPA), a non-competitive inhibitor, is used clinically to prevent organ transplant rejection by selectively blocking lymphocyte proliferation. However, drug resistance and isoform-specific effects drive ongoing research into next-generation inhibitors. Recombinant IMPDH2 also aids in studying mutations linked to retinal degeneration (e.g., retinitis pigmentosa) and viral replication mechanisms, as many pathogens depend on host guanine nucleotides.

Overall, recombinant IMPDH2 serves as a vital tool for bridging molecular insights with therapeutic development, highlighting its dual role in basic research and biomedical applications.

CSMD1 (CUB and Sushi Multiple Domains 1) is a large transmembrane protein encoded by the *CSMD1* gene, primarily expressed in epithelial and neuronal tissues. It belongs to the complement control protein (CCP) family, characterized by multiple CUB (C1r/C1s, Uegf, Bmp1) and sushi (complement-binding) domains, which are implicated in protein-protein interactions and regulation of immune responses. CSMD1 is thought to act as a tumor suppressor, with frequent genomic deletions or mutations observed in cancers, including head and neck squamous cell carcinoma, colorectal cancer, and glioblastoma. Its loss is associated with poor prognosis, suggesting a role in modulating cell adhesion, proliferation, and immune surveillance.

Recombinant CSMD1 protein is engineered to study its biological functions and therapeutic potential. Typically produced in mammalian or insect cell systems to ensure proper post-translational modifications, the recombinant protein retains key structural domains necessary for ligand binding and signaling. Researchers utilize it to investigate interactions with complement pathways, extracellular matrix components, or receptors involved in cell migration and apoptosis. Additionally, it serves as a tool for developing diagnostic assays or antibody production targeting CSMD1 in cancer biomarkers. Studies also explore its potential in restoring tumor-suppressive functions in *CSMD1*-deficient cancers. Despite progress, the full mechanistic landscape of CSMD1 remains unclear, highlighting the importance of recombinant protein-based approaches in elucidating its role in health and disease.