Lipofuscin Formation Catalyzed by the Milk Protein β-Lactoglobulin: Lysine Residues in Cycloretinal Synthesis

Vishruth Gowda, Jennifer Foulke-Abel, Hillary Agbo, Bennie J. Bench, Jooyeon Chae, William Russell, Coran M.H. Watanabe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 all-trans-retinal to cycloretinal both in vitro and in vivo. 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 in vivo. In the long term, these studies may pave the way for drug development and inhibitor design as an early treatment regimen for AMD.

Original languageEnglish (US)
Pages (from-to)5715-5719
Number of pages5
JournalBiochemistry
Volume56
Issue number43
DOIs
StatePublished - Oct 31 2017
Externally publishedYes

Fingerprint

Lipofuscin
Lactoglobulins
Milk Proteins
Macular Degeneration
Lysine
Biocatalysis
Mutagenesis
Poisons
Biosynthesis
Site-Directed Mutagenesis
Catalysis
Byproducts
Retina
Catalyst activity
Binding Sites
Peptides
Substrates
Pharmaceutical Preparations
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lipofuscin Formation Catalyzed by the Milk Protein β-Lactoglobulin : Lysine Residues in Cycloretinal Synthesis. / Gowda, Vishruth; Foulke-Abel, Jennifer; Agbo, Hillary; Bench, Bennie J.; Chae, Jooyeon; Russell, William; Watanabe, Coran M.H.

In: Biochemistry, Vol. 56, No. 43, 31.10.2017, p. 5715-5719.

Research output: Contribution to journalArticle

Gowda, Vishruth ; Foulke-Abel, Jennifer ; Agbo, Hillary ; Bench, Bennie J. ; Chae, Jooyeon ; Russell, William ; Watanabe, Coran M.H. / Lipofuscin Formation Catalyzed by the Milk Protein β-Lactoglobulin : Lysine Residues in Cycloretinal Synthesis. In: Biochemistry. 2017 ; Vol. 56, No. 43. pp. 5715-5719.
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