2o3q

Structural Basis for Formation and Hydrolysis of Calcium Messenger Cyclic ADP-ribose by Human CD38

spinqualitylabelsall models 2o3q, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2o3q is a 2 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 1.98Å Ligands: CXR 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 Human CD38 is a multifunctional ectoenzyme responsible for catalyzing the conversions from nicotinamide adenine dinucleotide (NAD) to cyclic ADP-ribose (cADPR) and from cADPR to ADP-ribose (ADPR). Both cADPR and ADPR are calcium messengers that can mobilize intracellular stores and activate influx as well. In this study, we determined three crystal structures of the human CD38 enzymatic domain complexed with cADPR at 1.5-A resolution, with its analog, cyclic GDP-ribose (cGDPR) (1.68 A) and with NGD (2.1 A) a substrate analog of NAD. The results indicate that the binding of cADPR or cGDPR to the active site induces structural rearrangements in the dipeptide Glu(146)-Asp(147) by as much as 2.7 A) providing the first direct evidence of a conformational change at the active site during catalysis. In addition, Glu(226) is shown to be critical not only in catalysis but also in positioning of cADPR at the catalytic site through strong hydrogen bonding interactions. Structural details obtained from these complexes provide a step-by-step description of the catalytic processes in the synthesis and hydrolysis of cADPR. Structural basis for formation and hydrolysis of the calcium messenger cyclic ADP-ribose by human CD38.,Liu Q, Kriksunov IA, Graeff R, Lee HC, Hao Q J Biol Chem. 2007 Feb 23;282(8):5853-61. Epub 2006 Dec 20. PMID:17182614 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cluster of Differentiation CD38

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