Structural and mechanistic insights into lunatic fringe from a kinetic analysis of enzyme mutants.

ABSTRACT: The Notch receptor is critical for proper development where it orchestrates numerous cell fate decisions. The Fringe family of beta1,3-N-acetylglucosaminyltransferases are regulators of this pathway. Fringe enzymes add N-acetylglucosamine to O-linked fucose on the epidermal growth factor repeats of Notch. Here we have analyzed the reaction catalyzed by Lunatic Fringe (Lfng) in detail. A mutagenesis strategy for Lfng was guided by a multiple sequence alignment of Fringe proteins and solutions from docking an epidermal growth factor-like O-fucose acceptor substrate onto a homology model of Lfng. We targeted three main areas as follows: residues that could help resolve where the fucose binds, residues in two conserved loops not observed in the published structure of Manic Fringe, and residues

SUBMITTER: Luther KB 

PROVIDER: S-EPMC2631955 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature