Human retinoblastoma binding protein 9,a serine hydrolase implicated in pancreatic cancers

Human retinoblastoma binding protein 9 (rbbp9) is an interacting partner of the retinoblastoma susceptibility protein (rb). rbbp9 is a tumor-associated protein required for pancreatic neoplasia,affects cell cycle control,and is involved in the tgf- α/βsignalling pathway. sequence analysis suggests that rbbp9 belongs to the α/βhydrolase superfamily of enzymes. the serine hydrolase activity of rbbp9 is required for development of pancreatic carcinomas in part by inhibiting tgf-α/βantiproliferative signaling through suppressing smad2/3 phosphorylation. the crystal structure of human rbbp9 confirms the α/β hydrolase fold,with a six-stranded parallel β-sheet flanked by β helixes. the structure of rbbp9 resembles that of the yden protein from bacillus subtilis,which is suggested to have carboxylesterase activity. rbbp9 contains a ser75-his165-asp138 catalytic triad,situated in a prominent pocket on the surface of the protein. the side chains of the lxcxe sequence motif that is important for interaction with rb is mostly buried in the structure. structure-function studies of rbbp9 suggest possible routes for novel cancer drug discovery programs. © 2012 bentham science publishers.