3dzf

Crystal structure of human CD38 extracellular domain complexed with a covalent intermediate, ara-F-ribose-5'-phosphate

spinqualitylabelsall models 3dzf, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3dzf is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.01Å Ligands: RF5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Enzymatic utilization of nicotinamide adenine dinucleotide (NAD) has increasingly been shown to have fundamental roles in gene regulation, signal transduction, and protein modification. Many of the processes require the cleavage of the nicotinamide moiety from the substrate and the formation of a reactive intermediate. Using X-ray crystallography, we show that human CD38, an NAD-utilizing enzyme, is capable of catalyzing the cleavage reactions through both covalent and noncovalent intermediates, depending on the substrate used. The covalent intermediate is resistant to further attack by nucleophiles, resulting in mechanism-based enzyme inactivation. The noncovalent intermediate is stabilized mainly through H-bond interactions, but appears to remain reactive. Our structural results favor the proposal of a noncovalent intermediate during normal enzymatic utilization of NAD by human CD38 and provide structural insights into the design of covalent and noncovalent inhibitors targeting NAD-utilization pathways. Covalent and noncovalent intermediates of an NAD utilizing enzyme, human CD38.,Liu Q, Kriksunov IA, Jiang H, Graeff R, Lin H, Lee HC, Hao Q Chem Biol. 2008 Oct 20;15(10):1068-78. PMID:18940667 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cluster of Differentiation CD38

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