Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 53, Issue 10, Pages 4038-4049Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm1001106
Keywords
-
Categories
Funding
- Human Frontiers Science Program
- Institute of Biomedical Sciences, Academia Sinica
- NSC [NSC 95-2113-M-001-001]
Ask authors/readers for more resources
The ADP-ribosylating toxins (ADPRTs) and poly(ADP-ribose) polymerases (PARPs) are two important drug target protein families. Although the Y-X-10-Y motif for the diphtheria toxin group and the STS motif for the other ADPRTs have been found to recognize the NAD(+) substrate, it is not known (i) if these two different motifs share any structural similarity, (ii) the key forces/residues contributing to NAD(+) binding, and (iii) if they recognize the same or different NAD(+) conformations. Here, we show that even though the different toxin groups and PARPs share insignificant sequence identity, they share a similar 3D structure shaped like a scorpion (the scorpion motif) whose first three and last residues interact mainly with the NAD(+) nicotinamide ring via van der Waals forces. This locally conserved structure binds the nicotinamide mononucleotide moiety in a structurally conserved ringlike conformation. The biological implications/applications of locally conserved structures for toxins/PARPs and the nicotinamide mononucleotide are discussed.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available