Download MendeleyFacile chemoenzymatic synthesis of a novel stable mimic of NAD.
Dai, Z., Zhang, X.N., Nasertorabi, F., Cheng, Q., Pei, H., Louie, S.G., Stevens, R.C., Zhang, Y.(2018) Chem Sci 9: 8337-8342
- PubMed: 30568770
- DOI: https://doi.org/10.1039/c8sc03899f
- Primary Citation of Related Structures:
6EDR - PubMed Abstract:
Nicotinamide adenine dinucleotide (NAD + ) is an essential cofactor participating in a variety of important enzyme-catalyzed physiological and pathophysiological processes. Analogues of NAD + provide key and valuable agents for investigating NAD + -dependent enzymes. In this study, we report the preparation of a novel stable NAD + mimic, 4'-thioribose NAD + (S-NAD + ), using a facile and efficient chemoenzymatic approach. Substrate activity assays indicated the resulting S-NAD + is chemically inert to human CD38 and sirtuin 2 enzymes, but capable of participating in redox reactions in a manner similar to NAD + . X-ray crystallographic analysis revealed binding of S-NAD + to the active site of human CD38 and critical residues involved in leaving group activation and catalysis. By more closely mimicking NAD + in geometry and electrostatics, the generated S-NAD + offers a unique and important tool that can be extended to study enzymes utilizing NAD + .
Organizational Affiliation:
Department of Pharmacology and Pharmaceutical Sciences , School of Pharmacy , University of Southern California , 1985 Zonal Ave , Los Angeles , CA 90089 , USA . Email: [email protected].
