Nucleotide pyrophosphatase/phosphodiesterase family

General Nucleotide pyrophosphatase/phosphodiesterase (NPP)-type ectophosphodiesterases are found on the cell surface as type-I or type-II transmembrane proteins, as well as extracellular proteins (secreted or shedded). They hydrolyze pyrophosphate (EC 3.6.1.9) or phosphodiester bonds (EC 3.1.4.1) in a variety of extracellular compounds including nucleotides, (lyso)phospholipids and choline phosphate esters (Stephan et al., 2005 )

In venom, these proteins have not been highly studied, probably due to their apparent lack of pathophysiology associated with snake envenoming. Indeed, a phosphodiesterase (PDE) activity has been described in a wide variety of snake venoms, but only a few PDEs have been characterized, and there is no report of primary sequence analysis. Reports from transcriptomic studies on the presence of transcripts for PDEs are therefore only based on homology.

As a consequence, the role of PDEs in the venom is not well understood. However, there is a growing appreciation that venom PDEs and other enzymes may play a role in the generation of purine nucleosides which could, in addition to purines present in the venom itself, play a role in the overall pathophysiology of envenoming. The inhibition of platelet aggregation is one of the indirect activities of these proteins (Santoro et al., 2009, Peng et al., 2011, Al-Saleh et al., 2011 ).

Structure
Venom PDEs are basic enzymes with molecular masses ranging from 98 kDa to 140 kDa, and are highly glycosylated. They are mostly monomers, but homodimers (Mori et al., 1987 ), or heterodimers (non covalently-linked) (Peng et al., 2011 ) have also been described.