Journal
EMBO JOURNAL
Volume 20, Issue 22, Pages 6191-6202Publisher
WILEY
DOI: 10.1093/emboj/20.22.6191
Keywords
alternative splicing; crystallography; human enzyme; oligomeric assembly; UDPGlcNAc pyrophosphorylase
Categories
Ask authors/readers for more resources
The recently published human genome with its relatively modest number of genes has highlighted the importance of post-transcriptional and post-translational modifications, such as alternative splicing or glycosylation, in generating the complexities of human biology. The human UDP-N-acetylglucosamine (UDPGlcNAc) pyrophosphorylases AGX1 and AGX2, which differ in sequence by an alternatively spliced 17 residue peptide, are key enzymes synthesizing UDPG1cNAc, an essential precursor for protein glycosylation. To better understand the catalytic mechanism of these enzymes and the role of the alternatively spliced segment, we have solved the crystal structures of AGX1 and AGX2 in complexes with UDPG1cNAc (at 1.9 and 2.4 Angstrom. resolution, respectively) and UDPGaI1Ac (at 2.2 and 2.3 Angstrom resolution, respectively). Comparison with known structures classifies AGX1 and AGX2 as two new members of the SpsA-GnT I Core superfamily and, together with mutagenesis analysis, helps identify residues critical for catalysis. Most importantly, our combined structural and biochemical data provide evidence for a change in the oligomeric assembly accompanied by a significant modification of the active site architecture, a result suggesting that the two isoforms generated by alternative splicing may have distinct catalytic properties.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available