Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024141 (
systemic lupus erythematosus
)
44,322
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The quinolines have been used in the treatment of malaria, arthritis, and
lupus
for many years, yet the precise mechanism of their action remains unclear. In this study, we used a functional proteomics approach that exploited the structural similarities between the quinoline compounds and the purine ring of ATP to identify quinoline-binding proteins. Several quinoline drugs were screened by displacement affinity chromatography against the purine binding proteome captured with gamma-phosphate-linked ATP-Sepharose. Screening of the human red blood cell purine binding proteome identified two human proteins, aldehyde dehydrogenase 1 (ALDH1) and
quinone reductase 2
(
QR2
). In contrast, no proteins were detected upon screening of the Plasmodium falciparum purine binding proteome with the quinolines. In a complementary approach, we passed cell lysates from mice, red blood cells, or P. falciparum over hydroxychloroquine- or primaquine-Sepharose. Consistent with the displacement affinity chromatography screen, ALDH and
QR2
were the only proteins recovered from mice and human red blood cell lysate and no proteins were recovered from P. falciparum. Furthermore, the activity of
QR2
was potently inhibited by several of the quinolines in vitro. Our results show that ALDH1 and
QR2
are selective targets of the quinolines and may provide new insights into the mechanism of action of these drugs.
...
PMID:Discovery of novel targets of quinoline drugs in the human purine binding proteome. 1243 4
