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

ABSTRACT: 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-? signalling pathway. Sequence analysis suggests that RBBP9 belongs to the ?/? hydrolase superfamily of enzymes. The serine hydrolase activity of RBBP9 is required for development of pancreatic carcinomas in part by inhibiting TGF-? antiproliferative signaling through suppressing Smad2/3 phosphorylation. The crystal structure of human RBBP9 confirms the ?/? hydrolase fold, with a six-stranded parallel ?-sheet flanked by ? 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.

SUBMITTER: Vorobiev SM

PROVIDER: S-EPMC3677193 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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

Vorobiev Sergey M SM Huang Yuanpeng Janet YJ Seetharaman Jayaraman J Xiao Rong R Acton Thomas B TB Montelione Gaetano T GT Tong Liang L

Protein and peptide letters 20120201 2

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-β signalling pathway. Sequence analysis suggests that RBBP9 belongs to the α/β hydrolase superfamily of enzymes. The serine hydrolase activity of RBBP9 is required for development of pancreatic carcinomas in part by inhibiting TGF-β antiproliferative ...[more]

PMID: 21933118

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

Publications

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

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