This family contains homologues of nucleoside diphosphate kinases (NDPKs). They are designated NDP kinase homologue 5 (NDK-H5), and differ from other NDPKs by having a C-terminal Dpy-30 motif. Despite considerable sequence similarity to other NDPKs, and conservation of seven out of nine known functionally important residues [, , ], human NDK-H5 (nm23-H5) seems to lack NDP kinase activity []. The nature of the sequence features specific to the NDK-H5 as compared to other NDPKs suggests that it may be unable to form hexamers and instead have a dimeric structure, which may affect its catalytic activity.NDK-H5 is thought to be involved in early stages of spermatogenesis []. Heterologous expression of murine NDK-H5 (nm23-M5) in yeast cells confers protection from cell death induced by Bax, which is due to the generation of reactive oxygen species, and over-expression of nm23-M5 in fibroblasts alters cellular levels of several antioxidant enzymes including Gpx5 []. Therefore, nm23-M5 may play a role in late spermatogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species [].
Glutathione peroxidase (GSHPx) () is an enzyme that catalyses the reduction of hydroperoxides by glutathione []. Its main function is to protect against the damaging effect of endogenously formed hydroperoxides. In higher vertebrates, several forms of GSHPx are known, including a ubiquitous cytosolic form (GSHPx-1), a gastrointestinal cytosolic form (GSHPx-GI), a plasma secreted form (GSHPx-P), and an epididymal secretory form (GSHPx-EP). In mammals there are eight GPx, divided in two clusters, the classical GPx (GPx1, GPx2, GPx3, GPx5 and GPx6) and phospholipid hydroperoxide GPx (GPx4, GPx7 and GPx8). The classical GPx is multimeric (commonly tetrameric) and soluble, while the phospholipid hydroperoxide (PHGPx) is monomeric and often membrane-associated []. In addition to these characterised forms, the sequence of a protein of unknown function []has been shown to be evolutionary related to those of GSHPx's.In filarial nematode parasites, the major soluble cuticular protein (gp29) is a secreted GSHPx, which may provide a mechanism of resistance to the immune reaction of the mammalian host by neutralising the products of the oxidative burst of leukocytes []. The structure of bovine seleno-glutathione peroxidase has been determined []. The protein belongs to the α-β class, with a three layer(aba) sandwich architecture. The catalytic site of GSHPx contains a conserved residue which is either a cysteine or, in many eukaryotic GSHPx, a selenocysteine [].
