1 research outputs found
Lipofuscin Formation Catalyzed by the Milk Protein β‑Lactoglobulin: Lysine Residues in Cycloretinal Synthesis
Lipofuscins are toxic
autofluorescent byproducts of the visual
cycle. The accumulation of lipofuscins such as cycloretinal in the
retina is thought to play a role in the progression of age-related
macular degeneration (AMD). Intriguingly, the milk protein β-lactoglobulin
(BLG) can promote the cyclodimerization of <i>all-trans</i>-retinal to cycloretinal both <i>in vitro</i> and <i>in vivo</i>. Here, site-directed mutagenesis of BLG and mass
spectrometric analysis with substrate analogues demonstrate that lysine
residues play a key role in catalysis. It is also shown that catalytic
activity necessitates the presence of a physical binding site and
cannot be mediated by a peptide chain. These studies provide insight
into the mechanism of the cyclodimerization process and provide a
model system for biocatalysis and biosynthesis of cycloretinal <i>in vivo</i>. In the long term, these studies may pave the way
for drug development and inhibitor design as an early treatment regimen
for AMD