6EDR

Crystal Structure of Human CD38 in Complex with 4'-Thioribose NAD+

Summary for 6EDR

• Entry DOI: 10.2210/pdb6edr/pdb
• Descriptor: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1, [[(2~{R},3~{S},4~{R},5~{R})-5-(3-aminocarbonylpyridin-1-ium-1-yl)-3,4-bis(oxidanyl)thiolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl hydrogen phosphate (3 entities in total)
• Functional Keywords: inhibitor, cd38, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 60888.47

Authors

Dai, Z.,Zhang, X.N.,Nasertorabi, F.,Cheng, Q.,Pei, H.,Louie, S.G.,Stevens, C.R.,Zhang, Y. (deposition date: 2018-08-10, release date: 2018-11-21, Last modification date: 2024-11-20)

Primary citation

Dai, Z.,Zhang, X.N.,Nasertorabi, F.,Cheng, Q.,Pei, H.,Louie, S.G.,Stevens, R.C.,Zhang, Y.
Facile chemoenzymatic synthesis of a novel stable mimic of NAD.
Chem Sci, 9:8337-8342, 2018

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.

PubMed: 30568770
DOI: 10.1039/c8sc03899f

Experimental method

X-RAY DIFFRACTION (2.4 Å)