Recently, it was shown that sulfasalazine and its metabolite sulfapyridine are potent inhibitors of sepiapterin reductase (SPR)
Sepiapterin reduction was measured by decreases in sepiapterin absorbance at 420 nm
Reactions were run with increasing concentrations of sulfasalazine in the presence of 25 mM (a), 50 mM (b), or 75 mM (c) sepiapterin
, 2015)
Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism
The mechanism of action of sulfasalazine, an anti-inflammatory drug used against inflammatory bowel diseases and rheumatoid arthritis is, despite its medical importance, still not well understood
Pull-down of sepiapterin reductase (SPR) by immobilized sulfasalazine from mammalian cell extracts of cells expressing SPR with a V5 epitope tag
Crystal structure of human sepiapterin reductase in complex with sulfasalazine: Source: Homo sapiens
Inhibition of SPR leads to the reduced levels of dihydrobiopterin (BH2) and Sepiapterin reductase inhibition selectively reduces inflammatory joint pain and increases urinary sepiapterin
To be published
The crystal structure of xanthurenic acid bound to the active site of SPR reveals why among all kynurenine pathway metabolites xanthurenic acid is the most potent SPR inhibitor
(b) Structure of sulfasalazine and the BG derivative used for three hybrid The phenotypic spectrum of sepiapterin reductase deficiency (SRD), which ranges from significant motor and cognitive deficits to only minimal findings, has not been completely elucidated
1 A) (1)
Virtual screening was executed against a publicly available x-ray crystal structure of sepiapterin reductase