4 research outputs found
A step towards understanding of the molecular basis of ligand promiscuity in the aminoglycoside modifying enzymes
Aminoglycosides have proven very useful in the treatment of infections; lately their effectiveness has been greatly reduced due to increasing resistance. Among many known mechanisms of resistance to aminoglycosides, enzymatic modification is the most prevailing. More than 14 aminoglycoside -N3-acetyltransferases- a class of aminoglycoside modifying enzymes, are known today. This study focuses on a pair of acetyl transferases: The aminoglycoside-N3- acetyltransferase IIIb (AAC-IIIb) and the aminoglycoside-N3- acetyltransferase IIa (AAC-IIa). AAC-IIa and AAC-IIIb are very similar in their amino acid sequence and structure – yet they have a strong difference in their substrate selectivity, kinetic and thermodynamic properties. This work represents a comparative study of these two enzymes in an effort to determine thermodynamic basis of the differential substrate profiles of AAC-IIa to AAC-IIIb
Effects of Branched O‑Glycosylation on a Semiflexible Peptide Linker
Glycosylation is an essential modification
of proteins and lipids
by the addition of carbohydrate residues. These attached carbohydrates
range from single monomers to elaborate branched glycans. Here, we
examine how the level of glycosylation affects the conformation of
a semiflexible peptide linker using the example of the hinge peptide
from immunoglobulin A. Three sets of atomistic models of this hinge
peptide with varying degrees of glycosylation are constructed to probe
how glycosylation affects the physical properties of the linker. We
found that glycosylation greatly altered the predominant conformations
of the peptide, causing it to become elongated in reference to the
unglycosylated form. Furthermore, glycosylation restricts the conformational
exploration of the peptide. At the residue level, glycans are found
to introduce a bias for the formation of more extended secondary structural
elements for glycosylated serines. Additionally, the flexibility of
this semiflexible proline-rich peptide is significantly reduced by
glycosylation