Guest Open Access Plus | Free Content | About | Sign in | New Users: Sign up | Mark List  

Protein & Peptide Letters

Volume 19 Issue 2
ISSN: 0929-8665
eISSN: 1875-5305

 

   All Titles

  Human Retinoblastoma Binding Protein 9, a Serine Hydrolase Implicated in Pancreatic Cancers
  pp.194-197 (4) Authors: Sergey M. Vorobiev, Yuanpeng Janet Huang, Jayaraman Seetharaman, Rong Xiao, Thomas B. Acton, Gaetano T. Montelione, Liang Tong
 
 
      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-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 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 α 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.

 
  Keywords: α/β hydrolase, pancreatic cancer, protein structure, structural genomics, RBBP9, antiproliferative, Smad2/3 phosphorylation, Bacillus subtilis, Ser75, emetine, E-cadherin
  Affiliation: Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY 10027.
 
  Key: New Content Free Content Open Access Plus Subscribed Content

Bentham Science Publishers
www.benthamscience.com

 

  Copyright © 1994 - 2014   Bentham Science Publishers