Fluorometric studies of ligand-induced conformational changes of CD38

Alteration of enzymatic properties of cell-surface antigen CD38 by agonistic anti-CD38 antibodies that prolong B cell survival and induce activation

“…It is therefore possible that anti-mouse CD38 mAbs and anti-human CD38 mAbs induce similar gross conformational changes in CD38, although the structure of the catalytic site is more significantly affected in the case of mouse CD38. It should be noted that the magnitude of the change in intrinsic fluorescence of mouse CD38 by NAD + is more profound than that of human CD38 [39]. Considering the potent agonistic action [2,37,64], the effect of anti-mouse CD38 antibody NIM-R5 on the catalytic activity should be studied in future work.…”

“…CD38 ligation by IB4 in OP-1 human immature B cell lines does not affect the amount of ADPR, nicotinamide or cADPR during a 10-60 min incubation [6], while NAD + suppresses the trypsin-sensitivity of the epitopes for the anti-human CD38 antibodies HB7, T16 and IB4 [38]. Since the epitopes of these antibodies are located in the carboxyl terminus of CD38 [63], a ligand-induced conformational change in human CD38 [39] implies an intramolecular interaction between the carboxyl terminus and the catalytic site. Although mapping of the epitopic sites of CS/2 and clone 90 is ongoing, a preliminary experiment suggested that Figure 7 Effect of CS/2 and clone 90 mAbs on enzymatic properties of FLAG-CD38 and cell-surface CD38 with and without secondary cross-linking.…”

“…Since NAD + suppresses the trypsin-sensitivity of CD38 [38] and decreases the intrinsic fluorescence of CD38 [39], the conformation of CD38 changes during the catalytic reaction. Thus, it is possible that the conformational change of CD38 upon CD38 ligation influences the catalytic properties of CD38.…”

Inhibitory effect of different product analogues on β-alanine synthase: A thermodynamic and fluorescence analysis

“…A tryptophan (Trp218) appears in the region where the binding site is allocated, and thus it must be buried by the conformational change triggered upon inhibitor binding (figure 5 bottom). The decrease in fluorescence intensity due to inhibitor binding could be explained by the proximity of this residue to the negative charge of the carboxylate moiety of Asp289 in the closed structure (or even to that of the inhibitor), thereby reducing its fluorescence quantum yield [27,28].…”

ADP-Ribosyl Cyclase as a Therapeutic Target for Central Nervous System Diseases

“…Also, slow conformational change may occur in the enzyme during hydrolysis of NAD + [11]. Interestingly, when functional activity resulted from binding of antibodies to discrete domains of human CD38 was assessed, dependence of the elicited response on the epitopes recognized by the individual monoclonal antibodies on leukocytes was found, thereby CD38-mediated signal transduction might be regulated by its conformational state by means of controlling interactions with different cell partners [102,114].…”