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

Ivan Koludarov; Steven D Aird

doi:10.7717/peerj.6154

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

PeerJ. 2019 Feb 6:7:e6154. doi: 10.7717/peerj.6154. eCollection 2019.

Authors

Ivan Koludarov¹, Steven D Aird²

Affiliations

¹ Ecology and Evolution Unit, Okinawa Institute of Science and Technology, Onna, Kunigami-gun, Okinawa, Japan.
² Ecology and Evolution Unit and Division of Faculty Affairs, Okinawa Institute of Science and Technology, Onna, Kunigami-gun, Okinawa, Japan.

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.

Keywords: 5′-nucleotidase; ADP-ribosyl cyclase; Adenosine; CD38; Exons; NAD glycohydrolase; NADase; Phosphodiesterase; Protobothrops mucrosquamatus genome; Snake venom.

Grants and funding

This work was supported by the Okinawa Institute of Science and Technology to the Ecology and Evolution Unit. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.