Structural highlights
Function[CD38_HUMAN] Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system. Publication Abstract from PubMedNicotinamide 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(+). Facile chemoenzymatic synthesis of a novel stable mimic of NAD().,Dai Z, Zhang XN, Nasertorabi F, Cheng Q, Pei H, Louie SG, Stevens RC, Zhang Y Chem Sci. 2018 Oct 15;9(44):8337-8342. doi: 10.1039/c8sc03899f. eCollection 2018 , Nov 28. PMID:30568770[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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