GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
TableEdit
PMID:27428513
You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki
See Help for Help on this wiki. See the documentation for how to use the table editor
Citation |
Yu, H, Takeuchi, H, Takeuchi, M, Liu, Q, Kantharia, J, Haltiwanger, RS and Li, H (2016) Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations. Nat. Chem. Biol. 12:735-40 |
---|---|
Abstract |
Rumi O-glucosylates the EGF repeats of a growing list of proteins essential in metazoan development, including Notch. Rumi is essential for Notch signaling, and Rumi dysregulation is linked to several human diseases. Despite Rumi's critical roles, it is unknown how Rumi glucosylates a serine of many but not all EGF repeats. Here we report crystal structures of Drosophila Rumi as binary and ternary complexes with a folded EGF repeat and/or donor substrates. These structures provide insights into the catalytic mechanism and show that Rumi recognizes structural signatures of the EGF motif, the U-shaped consensus sequence, C-X-S-X-(P/A)-C and a conserved hydrophobic region. We found that five Rumi mutations identified in cancers and Dowling-Degos disease are clustered around the enzyme active site and adversely affect its activity. Our study suggests that loss of Rumi activity may underlie these diseases, and the mechanistic insights may facilitate the development of modulators of Notch signaling. |
Links |
PubMed PMC4990500 Online version:10.1038/nchembio.2135 |
Keywords |
Animals; Biocatalysis; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Glucosyltransferases/chemistry; Glucosyltransferases/genetics; Glucosyltransferases/metabolism; Humans; Mice; Mutation; Protein Conformation |
public |
Cancel |