Qun Liu
New York Structural Biology Center
Abstract:
CD38 is a transmembrane receptor as well as a signaling enzyme in tissue and immune cells. As a signaling enzyme, CD38 can make use of substrate nicotinamide adenine dinucleotide (NAD) to biochemically produce cyclic ADP-ribose (cADPR) and ADP-ribose. It is interesting that the same enzyme can also degrade cADPR to ADP-ribose. cADPR is a key Ca2+ mobilization messenger in Ca2+ signaling. The NAD/CD38/cADPR signaling pathway is important for many physiological functions, for example smooth muscle contraction, hormone secretion, and inflammatory reaction. By utilizing NAD, CD38 also regulates NAD hemostasis in energy metabolism. Therefore CD38 plays a pivotal role in regulation of hemostasis of NAD and cADPR. A number of diseases and disorders, including obesity, infection, asthma and autism have been directly or indirectly ascribed to the NAD/CD38/cADPR signaling pathway. To understand mechanism of CD38 in the pathway, we used X-ray crystallography as a tool to study its delicate structures and chemistry. Our crystallographic snapshots along the reaction pathway allow visualization and characterization of the reactions at atomic resolution. Results from X-ray crystallography also provide substantial insights into the design of potent inhibitors with potential applications in pharmacological and cellular research.
2009 Run
Sept. 23rd to Nov. 10th
