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Creative Biostructure can provide custom MemPro™ gene-to-structure services for a wide range of membrane proteins such as the hypoxia-induced proteins. Our experienced scientists can perform the production, purification and characterization of membrane proteins. We can also analyze the structure of these hypoxia-induced proteins by X-ray, Cryo-Electron Microscopy (cryo-EM), Nuclear Magnetic Resonance (NMR) and Electron Crystallography.
Figure 1. Schematic of human carbonic anhydrase (CA) IV-membrane interaction.
Mammals has a primary mechanism that responds to reduced O2 (hypoxia) through hyperventilation, which enhances O2 delivery to cells by increasing arterial O2 tension. The hyperventilation that occurs during hypoxia is mediated by the O2-sensitive (type I) cells in the carotid body. In this stage, tyrosine hydroxylase is biosynthesized and enhanced in the carotid body and adrenal gland during hypoxia. On the other hand, It has been reported that Hypoxia is a predictor of poor prognosis in breast cancer. The features of tumors expressing hypoxic are associated with a higher incidence of resistance to radiotherapy. Hypoxia-induced proteins are proteins evolved in the development of hypoxic microenvironments, including carbonic anhydrase 9 (CA9/CAIX), carbonic anhydrase XII (CAXII), hypoxia-inducible gene 2 protein (HIG2) and so on. CAIX is considered to be one of the best cellular biomarkers of hypoxia. This protein has been found to increase in low oxygen environment of renal cell carcinomas (RCCs) and become a cancer-specific therapeutic target in the clinical trials. The expression of these membrane-bound proteins such as CAIX and CAXII are modulated by the hypoxia inducible factors (HIF). Meanwhile, HIG2 is a trans-membrane protein with a molecular weight of 7 kD and is found to be expressed during tumor development. These examples suggest that hypoxia-induced proteins play a critical role in therapeutics and pharmaceutics.
Creative Biostructure has many years of experience in the overexpression, purification and characterization of membrane proteins. Creative Biostructure can provide custom MemPro™ membrane protein gene-to-structure services, please click for more information. We can also provide various custom MemPro™ membrane protein production services. Please feel free to contact us for a detailed quote.
M. L. Norris and D. E. Millhorn (1995). Hypoxia-induced Protein Binding to O2-responsive Sequences on the Tyrosine Hydroxylase Gene. J. Biol. Chem., 270: 23774-23779.
M. Veronique, et al. (2012). Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer. Breast Cancer Res. Treat, 136(1): 76-75.
T. Stams, et al. (1996). Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-Å resolution. Proc. Natl. Acad. Sci., 93: 13589–13594.