| First Author | Zhou HL | Year | 2023 |
| Journal | Cell | Volume | 186 |
| Issue | 26 | Pages | 5812-5825.e21 |
| PubMed ID | 38056462 | Mgi Jnum | J:344183 |
| Mgi Id | MGI:7572641 | Doi | 10.1016/j.cell.2023.11.009 |
| Citation | Zhou HL, et al. (2023) An enzyme that selectively S-nitrosylates proteins to regulate insulin signaling. Cell 186(26):5812-5825.e21 |
| abstractText | Acyl-coenzyme A (acyl-CoA) species are cofactors for numerous enzymes that acylate thousands of proteins. Here, we describe an enzyme that uses S-nitroso-CoA (SNO-CoA) as its cofactor to S-nitrosylate multiple proteins (SNO-CoA-assisted nitrosylase, SCAN). Separate domains in SCAN mediate SNO-CoA and substrate binding, allowing SCAN to selectively catalyze SNO transfer from SNO-CoA to SCAN to multiple protein targets, including the insulin receptor (INSR) and insulin receptor substrate 1 (IRS1). Insulin-stimulated S-nitrosylation of INSR/IRS1 by SCAN reduces insulin signaling physiologically, whereas increased SCAN activity in obesity causes INSR/IRS1 hypernitrosylation and insulin resistance. SCAN-deficient mice are thus protected from diabetes. In human skeletal muscle and adipose tissue, SCAN expression increases with body mass index and correlates with INSR S-nitrosylation. S-nitrosylation by SCAN/SNO-CoA thus defines a new enzyme class, a unique mode of receptor tyrosine kinase regulation, and a revised paradigm for NO function in physiology and disease. |
