A Genetically Encoded Redox-Active Nicotinamide Amino Acid.
| Autor: | Pigula ML; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Ban Y; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., You H; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Schultz PG; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Biochemistry [Biochemistry] 2024 Dec 17; Vol. 63 (24), pp. 3184-3188. Date of Electronic Publication: 2024 Nov 25. |
| DOI: | 10.1021/acs.biochem.4c00530 |
| Abstrakt: | Nicotinamide-containing cofactors play an essential role in many enzymes that catalyze two-electron redox reactions. However, it is difficult to engineer nicotinamide binding sites into proteins due to the extended nature of the cofactor-protein interface and the precise orientation of the nicotinamide moiety required for efficient electron transfer to or from the substrate. To address these challenges, we genetically encoded a noncanonical amino acid (ncAA) bearing a nicotinamide side chain in bacteria. This redox-active amino acid, termed Nic1, exhibits similar electrochemical properties to the natural cofactor nicotinamide adenine dinucleotide (NAD + ). Nic1 can be reversibly reduced and oxidized using chemical reagents both free in solution and when incorporated into a model protein. This genetically encodable cofactor can be introduced into proteins in a site-specific fashion and may serve as a tool to study electron-transfer mechanisms in enzymes and to engineer redox-active proteins. |
| Databáze: | MEDLINE |
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