Snake venom NAD glycohydrolases: primary structures, genomic location, and gene structure

Abstract

NAD glycohydrolase (EC 3.2.2.5) (NADase) sequences have been identified in 10 elapid and crotalid venom gland transcriptomes, eight of which are complete. These sequences show very high homology, but elapid and crotalid sequences also display consistent differences. As in Aplysia kurodai ADP-ribosyl cyclase and vertebrate CD38 genes, snake venom NADase genes comprise eight exons; however, in the Protobothrops mucrosquamatus genome, the sixth exon is sometimes not transcribed, yielding a shortened NADase mRNA that encodes all six disulfide bonds, but an active site that lacks the catalytic glutamate residue. The function of this shortened protein, if expressed, is unknown. While many vertebrate CD38s are multifunctional, liberating both ADP-ribose and small quantities of cyclic ADP-ribose (cADPR), snake venom CD38 homologs are dedicated NADases. They possess the invariant TLEDTL sequence (residues 144–149) that bounds the active site and the catalytic residue, Glu228. In addition, they possess a disulfide bond (Cys121–Cys202) that specifically prevents ADP-ribosyl cyclase activity in combination with Ile224, in lieu of phenylalanine, which is requisite for ADPR cyclases. In concert with venom phosphodiesterase and 5′-nucleotidase and their ecto-enzyme homologs in prey tissues, snake venom NADases comprise part of an envenomation strategy to liberate purine nucleosides, and particularly adenosine, in the prey, promoting prey immobilization via hypotension and paralysis.

Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

“…Analyses of hydropathicity and charge of KLK1 regulatory loops (34) were calculated using the ProtParam tool of the ExPASy Bioinformatics Resource Portal, with statistical comparisons performed using unpaired 2-tailed t tests in GraphPad Prism (La Jolla, CA). De novo annotation of KLK exons and synteny comparisons of mammalian genomic data were undertaken as recently described (62). Ancestral trait reconstructions were performed with Ape (63) and Phytools (64) in R, and the marginal ancestral states (empirical Bayesian posterior probabilities) were estimated for each node in a eulipotyphlan species tree derived from prior studies (19, 37).…”

Discovering Biological Conflict Systems Through Genome Analysis: Evolutionary Principles and Biochemical Novelty

“…One such mechanism targets NAD + -the energy currency, cosubstrate for redox reactions, and substrate in DNA replication and repair (Figure 1). Thus, effectors known as NADases, which degrade NAD + into ADP-ribose (ADPr) and nicotinamide, are another shared kind of molecular weaponry from animal venoms to prokaryotic toxins (40,(49)(50)(51). Several structurally unrelated domains possess NADase activity: One common type is related to ARTs (40,51,52), while the other prevalent type is the TIR domain (50,53).…”

Adenosine diphosphate ribose cyclase: An important regulator of human pathological and physiological processes

“…Scientists have proposed a "partition" reaction scheme to cADPR/ADPR via ADPRC, that is, its relative cyclization/hydrolysis rate constant ratio, which determines the synthesis of its cADPR and ADPR. For invertebrates, NAD transformation tends to be the mechanism by which cADPR forms before ADPR (Koludarov & Aird, 2019). In addition, NAADP, another metabolite of ADPRC, synthesized by the base exchange reaction of NADP with nicotinamide.…”