Homology modeling and functional annotation of bubaline pregnancy associated glycoprotein 2

Our study describes an in silico derived 3D model for bubaline pregnancy associated glycoprotein 2. Structure-activity features of the protein were characterized, and functional studies predict bubaline pregnancy associated glycoprotein 2 as an inducible, extra-cellular, non-essential, N-glycosylated, aspartic pro-endopeptidase that is involved in down-regulation of complement pathway and immunity during pregnancy. The protein is also predicted to be involved in nutritional processes, and apoptotic processes underlying fetal morphogenesis and re-modeling of feto-maternal tissues.The structural and functional annotation of buPAG2 shall allow the designing of mutants and inhibitors for dissection of the exact physiological role of the protein.Pregnancy associated glycoproteins (PAGs) were first isolated in 1982 by Butler and co-workers from the outer epithelial cell layer (chorion/ trophectoderm) of the bovine feto-maternal membranes where they are secreted by binucleate cells [1,2]. Subsequently, PAGs have been isolated from several other species like sheep, goat, buffalo, cat, pig and horse. Presently, more than 100 PAG genes are known in ruminants, forming a very diverse family of glycoproteins that are variably expressed at different stages of gestation, starting about 7th day post-fertilization onwards, largely in the pre-placental trophoblast, and post-implantation trophectoderm [3]. Also known as pregnancy specific protein-B (PSPB) or pregnancy specific protein (PSP)-60, these are putatively known to act as immunosuppressants that allow the immunological acceptance of the embryo by the dam. The presence of the products of binucleate cells in maternal circulation has also been correlated with placentogenesis and placental re-modeling [4]. However, the exact structure and function of the gene product remains largely undetermined; limitations on obtaining purified PAG preparations being the major bottleneck. PAGs show high sequence homology as a group, and also to