Bullying and Autism

Woods, Alisa G.

doi:10.4172/2165-7890.1000e118

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“…Syn and anti refer to values of 0° and 180° with respect to the H2-C2-C-N torsion angle; however, as hydrogen atoms are not routinely reported in crystal structures, these orientations have alternatively been defined here in terms of C1-C2-N-C for which syn = −60° and anti = 120°. A 3D structure for GlcNAc-β-O-Ser was built using the GLYCAM webtool ( Woods 2005–2013 ) and modified using Maestro ( Maestro 2011 ) to generate three rotamers of the serine side chain ( χ 1 = 40.7, 170.6, and −49.1°, see Figure 5 B), as identified from the Dynameomics database ( Day et al 2003 ; Beck et al 2008 ; Kehl et al 2008 ; Simms et al 2008 ). The N- and C-terminal residue was capped for all glycopeptides with an acetyl (ACE) or N -methyl (NME) group, respectively.…”

Section: Methodsmentioning

confidence: 99%

Defining the structural origin of the substrate sequence independence of O-GlcNAcase using a combination of molecular docking and dynamics simulation

et al. 2013

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Protein glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine/threonine residues in nucleocytoplasmic proteins. O-GlcNAc has been shown to play a role in many different cellular processes and O-GlcNAcylation is often found at sites that are also known to be phosphorylated. Unlike phosphorylation, O-GlcNAc levels are regulated by only two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA). So far, no obvious consensus sequence has been found for sites of O-GlcNAcylation. Additionally, O-GlcNAcase recognizes and cleaves all O-GlcNAcylated proteins, independent of their sequence. In this work, we generate and analyze five models of O-GlcNAcylated peptides in complex with a bacterial OGA. Each of the five glycopeptides bind to OGA in a similar fashion, with OGA–peptide interactions primarily, but not exclusively, involving the peptide backbone atoms, thus explaining the lack of sensitivity to peptide sequence. Nonetheless, differences in peptide sequences, particularly at the −1 to −4 positions, lead to variations in predicted affinity, consistent with observed experimental variations in enzyme kinetics. The potential exists, therefore, to employ the present analysis to guide the development glycopeptide-specific inhibitors, or conversely, the conversion of OGA into a reagent that could target specific O-GlcNAcylated peptide sequences.

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