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

Ivan Koludarov,Steven D Aird

doi:10.7717/peerj.6154

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.

Highlights

More than 60 years ago, Bhattacharya (1953) reported that when Bungarus fasciatus venom is incubated with NAD, it releases nicotinamide
The NCBI Protein site was searched for vertebrate NAD glycohydrolase sequences and the sequence of chicken ADP-ribosyl cyclase (ADQ89191.1), known as CD38, was downloaded for use as a query sequence
A partial (30-residue), unidentified sequence occurs in the Ophiophagus hannah genome (L345_15802). The former sequences were aligned with CD38 sequences from Gallus gallus, Xenopus laevis, Anolis carolinensis, and Homo sapiens, using Geneious (Fig. 1)

Summary

Introduction

More than 60 years ago, Bhattacharya (1953) reported that when Bungarus fasciatus venom is incubated with NAD, it releases nicotinamide. This constituted the first evidence that some snake venoms contain an NAD glycohydrolase (NADase) (EC 3.2.2.5). Like many other non-toxic enzymes, its presence in venoms seemed enigmatic until Aird (2002) proposed that purine nucleosides comprise core elements of the envenomation strategies of most advanced venomous snakes. Adenosine is important because of its hypotensive and neuroprotective (neurosuppressive) activities. How to cite this article Koludarov I, Aird SD. Snake venom NAD glycohydrolases: primary structures, genomic location, and gene structure.

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Conclusion