3RDE

Crystal structure of the catalytic domain of porcine leukocyte 12-lipoxygenase

Summary for 3RDE

• Entry DOI: 10.2210/pdb3rde/pdb
• Descriptor: Arachidonate 12-lipoxygenase, 12S-type, POTASSIUM ION, FE (II) ION, ... (5 entities in total)
• Functional Keywords: lipoxygenase, c-terminal domain, protein-inhibitor complex, 4-(2-oxapentadeca-4-yne)phenylpropanoic acid, lipoxygenase catalytic domain, dioxygenase, fe, leukocyte, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Sus scrofa (pigs,swine,wild boar)
• Cellular location: Cytoplasm: P16469
• Total number of polymer chains: 4
• Total formula weight: 260800.54

Authors

Funk, M.O.,Xu, S.,Marnett, L.J.,Mueser, T.C. (deposition date: 2011-04-01, release date: 2012-04-18, Last modification date: 2023-09-13)

Primary citation

Xu, S.,Mueser, T.C.,Marnett, L.J.,Funk, M.O.
Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex identifies a substrate-binding channel for catalysis.
Structure, 20:1490-1497, 2012

PubMed Abstract: Lipoxygenases are critical enzymes in the biosynthesis of families of bioactive lipids including compounds with important roles in the initiation and resolution of inflammation and in associated diseases such as diabetes, cardiovascular disease, and cancer. Crystals diffracting to high resolution (1.9 Å) were obtained for a complex between the catalytic domain of leukocyte 12-lipoxygenase and the isoform-specific inhibitor, 4-(2-oxapentadeca-4-yne)phenylpropanoic acid (OPP). In the three-dimensional structure of the complex, the inhibitor occupied a new U-shaped channel open at one end to the surface of the protein and extending past the redox-active iron site that is essential for catalysis. In models, the channel accommodated arachidonic acid, defining the binding site for the substrate of the catalyzed reaction. There was a void adjacent to the OPP binding site connecting to the surface of the enzyme and providing a plausible access channel for the other substrate, oxygen.

PubMed: 22795085
DOI: 10.1016/j.str.2012.06.003

Experimental method

X-RAY DIFFRACTION (1.892 Å)