Structural and functional evaluation mammalian and plant lipoxygenases upon association with nanodics as membrane mimetics.

Ulusan S., Sheraj I., Stehling S., Ivanov I., Das A., Kühn H., ...Daha Fazla

Biophysical chemistry, cilt.288, ss.106855, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 288
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.bpc.2022.106855
  • Dergi Adı: Biophysical chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.106855
  • Anahtar Kelimeler: Lipoxygenase, Nanodisc, Enzyme activity, Inhibition, RETICULOCYTE LIPOXYGENASE, HYDRODYNAMIC RADIUS, DISORDERED PROTEIN, ARACHIDONIC-ACID, OXYGENATION, CALCIUM, 15-LIPOXYGENASE-1, 15S-LIPOXYGENASE, 5-LIPOXYGENASE, BINDING
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

Lipoxygenases (LOX) are a family lipid oxygenating enzymes that can generate bioactive lipids of clinical rele-vance from polyunsaturated fatty acids. Most LOXs display a Ca2+-dependent association with membranes for their activity. Nanodiscs (ND) are stable self-assembled discoidal fragments of lipid bilayers that can mimic the plasma membrane. In this study, we evaluated the association of mammalian 15-LOXs (ALOX15 and ALOX15B) and soybean LOX-1 with NDs (LOX-ND), their enzymatic activities and inhibition. Mammalian LOXs associated with NDs showed better retention of enzymatic function compared to soybean LOX-1. Treatment of both LOX-NDs and free enzymes with the pan-LOX inhibitor nordihydroguaiaretic acid (NDGA) showed an approxi-mately 5-fold more effective inhibition of the enzymes associated with NDs compared to the free form. NDs are easy to generate membrane mimics that can be used as an effective tool to determine enzymatic function and inhibition of membrane associated proteins.