Probing ligand-induced conformational changes of human CD38.

摘要: The lymphoid surface antigen CD38 is basically a NAD+glycohydrolase, which also involved in the metabolism of cyclic ADP-ribose. Besides, this ecto-enzyme has potential signalling roles T- and B-cells. Such multiple functions prompted us to study molecular dynamics protein especially relationship between its ecto-enzymatic active site epitope, i.e. binding most known anti-CD38 monoclonal antibodies. Both epitopic enzymatic sites were shown be degraded by proteases, such as trypsin or chymotrypsin. This sensitivity was almost entirely suppressed presence substrates inhibitors. reducing agents, dithiothreitol. Inhibitory ligands induced same resistance both against attack. triggers therefore conformational changes that shield some backbone bonds disulfide bridges against, respectively, proteolytic cleavage reduction. transconformation found moreover irreversibly take place after incubation with NAD+ epitope remained preserved, while activity lost. inactivation probably resulted from covalent trapping catalytically reactive intermediate (i.e. paracatalytic inactivation). These data have major implications knowledge structure, regard location their accessibility. Potential consequences plasticity should considered physiological signalling.