Abstract
Gangliosides are the sphingolipids containing sialic acids. Some enzymes recognize their sugar chain. It has been reported that gangliosides inhibit the activity of an enzyme NAD+ glycohydrolase(CD38), and that those with a tandem sialic acid in the sugar chain have the largest inhibitory effect. However, the mechanism at higher levels of structure has not been elucidated. The objective of our investigation is to clarify the cause of difference in the inhibitory effect in terms of three-dimensional structures and electronic structures of gangliosides. We assessed the similarity of the calculated structures of NAD+ and tandem sialic acid using CONFLEX, MM3 and PM3, on the assumption that CD38, an NAD+ reacting enzyme, cross-reacts with the tandem sialic acid in gangliosides. It was found that there were similarities in the distance between oxygen atoms having negative charges, the dipole moment, and HOMO between the POO--O-POO- in NAD+ and the two COO- groups in tandem sialic acid. A strong correlation between the orbital energy of HOMO and the magnitude of the inhibitory effect was also found. Our study suggests that CD38 recognizes the POO- groups in NAD+ and the two COO- groups in tandem sialic acid, which is consistent with the experimental results.
